Dear Dr. Samkovich,

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 05 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.

• 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,

Vibhuti Agrahari

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional 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

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering.

3. We note that your Data Availability Statement is currently as follows: “All relevant data are within the manuscript and its Supporting Information files.”

Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

For example, authors should submit the following data:

- The values behind the means, standard deviations and other measures reported;

- The values used to build graphs;

- The points extracted from images for analysis.

Authors do not need to submit their entire data set if only a portion of the data was used in the reported study.

If your submission does not contain these data, please either upload them as Supporting Information files or deposit them to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories.

If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If data are owned by a third party, please indicate how others may request data access.

4. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

[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?

Reviewer #1: Partly

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: No

Reviewer #2: Yes

**********

Reviewer #1: Comments and Queries from Reviewer

The topic of article presented is appreciative and study reports certain worthwhile information that can be considered useful for clinical translation in future. Data appears detailed and thorough. The author appears to have an appreciative effort in discussion section to provide thorough arguments regarding the study as well as its drawback and future prospects in discussion. Thus, it is a useful study to be reported. Although, there are a few suggestions and queries for the author, which are as follows:

1. https://journals.sbmu.ac.ir/jlms/article/view/47901/35787 (Transscleral Photodynamic Therapy with a Chlorin e6 Photosensitizer in a Rabbit Experimental Model of an Intraocular Mass Lesion: TS-PDT in experimental ocular mass lesion model).

a. The reviewer suggests the author to explain if this study is different from the given manuscript. If possible please share the manuscript PDF, as it is not accessible.

2. In the Line 179-181 (The therapeutic window and key parameters (laser power, power density, energy density, thermal dynamics) were first-ever systematically defined by correlating clinical, histological, and thermal responses in a controlled model)

a. Is the author sure about the claims mentioned above? Please also shed some light and explain about the clinical correlation other wise the author may modify the statement.

3. Twenty-one rabbits (3.0–3.5 kg) underwent ophthalmic screening. Procedures followed the 69 Declaration of Helsinki and Directive 2010/63/EU, with approval from the local Ethics Committee 70 of the Federal State Budgetary Scientific Institution “IEM” (Protocol No. 4/24, dated October 24, 71 2024).

a. This paragraph and like this other major content of the article has come under plagiarism indicating use of some AI software. The reviewer advise to the author to kindly re-check whole manuscript for the AI plagiarism and paraphrase the text.

4. The manuscript needs to review by author for reference citation correction (for example reference 5 or 6 doesn’t suggest correct citation for line 205, and First sentence specific reference needed instead of adding reference after paras.) likewise there are more. The references are at certain places not accurate or wrongly added.

5. Material method 2nd para lacks sentences wise specific references. Rather bunch of references added altogether after couple of sentences. This confuses readers to choose correct reference for specific context.

6. The reviewer suggests the author to kindly cite references next to each sentence where it is referred to, instead of citing a bunch of references after 2-3 sentences combined. It is only confusing the readers and not giving accurate information.

7. Introduction section lacks streamlined discussions rather puts useful information in random order in a way that the discussion topics abruptly shifts from one to another without any order. The author wants to share useful information but it needs to streamlined and described in orderly manner while connecting the dots as a storyline discussion.

8. Which species of rabbits selected for animal study?

9. This sentence is unclear. This sentence has missing to write “treatment Zones”.

a. Due to the rabbits’ globe size, two zones were possible with the 10 mm probe and three zones with the 5 mm probe.

10. The following sentences appears to be unclear. How 10 Rabbits have 20 right eyes or other 10 rabbits have 20 left eyes.

a. Rabbits were divided into two groups:

Group I (5 mm probe, 10 rabbits, 20 right eyes): 0.1 W, 0.17 W, 0.3 W; exposure 600 s. Group II (10 mm probe, 10 rabbits, 20 left eyes): : 0.3 W, 0.6 W; exposure 600 s.

11. Is the author sure to use the term “Clinical” in the abstract under the purpose section for “animal-based study”? if yes, please justify.

12. Among the three zones of used in the study using 5 mm probe, two (0.1 W, and 0.17 W) are discussed although, the discussion on zone 3 (0.3 W) appears to be lacking.

13. Histological changes on 10 mm probe of 0.3 W in fig 2C is missing.

14. Please explain in line 148 author mentioned the p value as p< 0.001, however, in the table 2 group 2 it is shown as p= 0.1, which one is correct?

15. The captions for fig 3A and Fig 3B are same!?

16. Table 3 column 5 heading show T10 – T0, but T5 – T0 is not added in the table, please explain the reason. What is the clinical significance of Scleral Temperature Changes? Please answer both queries separately.

Reviewer #2: This manuscript investigates transcleral photodynamic therapy with chlorine e6 in rabbits, focusing on the parameters of exposition and therapeutic window. Overall, the manuscript is well written, with a structured abstract and a concise and clear Introduction. The Material and Methods included the information on laser parameters, as expected, besides characteristics of transscleral, and chlorine e6 dosages, allowing the reproduction of the study.

Actually, I have a doubt on this section. At page 4, the authors describe that "Rabbits were divided into two groups: group I (5 mm probe, 10 rabbits, 20 right eyes): 0.197 W, 0.17 W, 0.3 W; exposure 600 s. group II (10 mm probe, 10 rabbits, 20 left eyes): 0.3 W, 0.6 W; exposure 600 s. One eye served as a control. Temperature was recorded at baseline, 5 min, and 10 min. ΔT was defined as the difference between baseline and 10-min readings."

The question is: how can 10 rabbits have 20 right eyes or 20 left eyes? I believe this is not correct. Please review/clarify. Tables legends must describe the statistical tests used.

The main limitations of the study are the use of healthy rabbit's eye to simulate the application of therapy aimed at tumor treatment. The model does not simulate the tumor microenvironment and a deeper discussion on the possible clinical application of the methodology presented in a healthy animal model should be provided. A deeper discussion on the main challenges of the study for a clinical application should be provided.

**********

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

**********

[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Attachments

Attachment

Submitted filename: Comment Plos 10052025.docx

Transscleral Photodynamic Therapy with a Chlorin e6: an Experimental Study of Exposure Parameters and Therapeutic Window

PONE-D-25-24966R1

Dear Dr. Samkovich,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

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,

Vibhuti Agrahari

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: (No Response)

Reviewer #2: After the first review round, the authors have correctly addressed all the flaws pointed out by the reviewers. In particular, I am delighted with the improvement in the manuscript quality achieved by the substantial changes made to the original text, as well as with the detailed answers to the reviewers' comments that the authors have provided, which justified the methodology and clarified my doubts. I don't have any other concerns to list.

**********

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

**********