Objective hyperemia and intraocular pressure changes following omidenepag isopropyl application

Kana Tokumo; Tsuyoshi Yoneda; Yuta Nakaniida; Ryota Aoki; Shunsuke Nakakura; Taro Baba; Naoki Okada; Ayaka Edo; Hiromitsu Onoe; Hideaki Okumichi; Kazuyuki Hirooka; Diane Sonassa; Hitoshi Tabuchi; Yoshiaki Kiuchi; Hirokazu Sakaguchi

doi:10.1371/journal.pone.0326187

Peer Review History

Original SubmissionOctober 14, 2024
Decision Letter - Natasha Gautam, Editor PONE-D-24-44578Objective hyperemia and intraocular pressure changes after application of omidenepag isopropylPLOS ONE Dear Dr. Tokumo, 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 is well drafted but there is a scope of improvement. Please submit your revised manuscript by Apr 19 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. 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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. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: - https://coek.info/pdf-cystoid-macula-edema-related-to-cataract-surgery-and-topical-prostaglandin-analo.html ? In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed 3. We note that your Data Availability Statement is currently as follows: “All relevant data are within the manuscript. 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Were there any patients in the study for whom omidenepag isopropyl was stopped due to hyperemia, or if the patients were so symptomatic that required artificial tear drops or additional intervention? [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? 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Reviewer #1: Yes ****** 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: Dear authors It is a nicely conducted study. It needs few modifications 1. Are the patients shifted from FP receptor to new drug only due to hyperemia or because of other complications of the drug? 2. Hyperemia indicates ocular surface inflammation. Table 2 shows few patients on multiple medications especially alpha agonists which can also be confounding to cause hyperemia. How do you substantiate this? 3. Are there any patients operated for glaucoma and then restarted on this new drug? Or there are any patient who have been operated for glaucoma but trab has failed and started on PGA but switched to new drug in question? 4. Table 1 shows no of glaucoma medications 1.8� 1.7 here SD is more than 1/3rd of MD which implies data is not normal , Hence need to be represented as MD with interquartile range. please redo this statistics. 5. When the age group mentioned s 61.2�16.7 how can u explain the developmental glaucoma , were they diagnosed and treated before and hence included here ? 6. Line 136, the statistic mentioned again is inappropriate as mentioned in statement 4 here. please do non parametric test and see and report. 7. Line 150 …… IOP was significantly reduced from 16.2�3.6 to 14.3�3.0. The distribution or range is overlapping how can one say it is statistically significant IOP drop? 8. Line 175 in discussion the mean onset time of hyperemia of 27�48.3 days and recovery time 32.1�37.6 days--- it is inappropriately represented.how can it be -21 days of starting medications – it is not rational. ****** 6. 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Revision 1
17 May 2025 Author Response Dear Editorial Team, Thank you for the opportunity to revise our manuscript. We have carefully addressed each of the journal’s requirements and the reviewers’ comments as detailed below. Journal Requirements 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. →Thank you.We have reformatted our manuscript to fully comply with the PLOS ONE style guidelines for both the main text and file-naming conventions, using the templates provided. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: https://coek.info/pdf-cystoid-macula-edema-related-to-cataract-surgery-and-topical-prostaglandin-analo.html →Thank you for pointing out. We have rephrased all overlapping passages (Lines 228–231) and ensured that every source which is our own and others is now properly cited or quoted. 3.We note that your Data Availability Statement is currently as follows: “All relevant data are within the manuscript. If additional data are needed, please contact the corresponding author, and they will be provided.” 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 →Thank you for pointing out. We confirm that all raw data necessary to reproduce our study results are included. We have uploaded the minimal data set. Values behind all summary statistics and graphs, plus extracted image data as Supporting Information files. Additional Editor Comment 1.Were there any patients in the study who discontinued omidenepag isopropyl due to hyperemia, or who required artificial tears or additional intervention because of symptoms? No patients discontinued omidenepag isopropyl because of hyperemia, and none required artificial tears or other interventions for ocular surface discomfort during the study period. →Thank you for asking us. Rather than restricting the switch to those troubled by conjunctival hyperemia, we informed all eligible patients that a new drug was available. Those who expressed a preference for the new therapy were switched from FP-receptor agonists to omidenepag isopropyl (Lines 93–96). 2.Hyperemia indicates ocular surface inflammation. Table 2 shows few patients on multiple medications especially alpha agonists which can also be confounding to cause hyperemia. How do you substantiate this? →Thank you for the question. In the switching group, only the FP receptor agonist was changed to omidenepag isopropyl; all other concomitant eye drops including alpha-agonists remained unchanged. Because we compared each patient’s hyperemia score before and after switching, any change is attributable to the FP-receptor agent switch. Statistical significance was tested with the Wilcoxon signed-rank test. 3. Are there any patients operated for glaucoma and then restarted on this new drug? Or there are any patient who have been operated for glaucoma but trab has failed and started on PGA but switched to new drug in question? →Thank you for the question. Yes. Some patients resumed omidenepag isopropyl after prior glaucoma surgery when further IOP reduction was needed; others began postoperative PGA therapy and later switched to the new drug. The number of surgically treated eyes is now listed in Table 1, and we clarify that previous surgeries included trabeculotomy and trabeculectomy (Lines 129–131). 4. Table 1 shows no of glaucoma medications 1.8±1.7 here SD is more than 1/3rd of MD which implies data is not normal , Hence need to be represented as MD with interquartile range. please redo this statistics. →Thank you for pointing out. We have replaced the mean ± SD with median (IQR): 1.5 (1.0–2.8) medications in the switching group. 5.When the age group mentioned s 61.2±16.7 how can u explain the developmental glaucoma , were they diagnosed and treated before and hence included here ? →Thank you for the question. The three developmental-glaucoma patients were aged 24, 28, and 31 at enrollment. All had been diagnosed and treated in childhood; two had undergone trabeculotomy. They currently remain on topical therapy. 6. Line 136, the statistic mentioned again is inappropriate as mentioned in statement 4 here. please do non parametric test and see and report. →Thank you for pointing out. We have replaced all parametric tests with the Wilcoxon signed-rank test where appropriate. 7. Line 150 …… IOP was significantly reduced from 16.2±3.6 to 14.3±3.0. The distribution or range is overlapping how can one say it is statistically significant IOP drop? →Thank you for the question. We now report IOP as median (IQR): New administration group: before 15.0 (13.5–18.5) mmHg; after 15.0 (11.0–16.5) mmHg (P = 0.03, Wilcoxon signed-rank test). Although the ranges overlap, the paired analysis shows a significant reduction. 8. Line 175 in discussion the mean onset time of hyperemia of 27±48.3 days and recovery time 32.1±37.6 days--- it is inappropriately represented. How can it be -21 days of starting medications – it is not rational. Response: Thank you for pointing out. The original source reported medians in addition to means, with a median time to onset of 12 days and a median time to recovery of 25 days. We rewrote the sentence in line 186-187. We appreciate the reviewers’ constructive suggestions and believe these revisions have substantially strengthened our manuscript. Thank you for considering our revised submission. Sincerely, Kana Tokumo Attachments Attachment Submitted filename: Response to reviwer.docx https://doi.org/10.1371/journal.pone.0326187.r002
Decision Letter - Natasha Gautam, Editor Objective hyperemia and intraocular pressure changes following omidenepag isopropyl application PONE-D-24-44578R1 Dear Dr. Tokumo, 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. If you have any questions relating to publication charges, 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, Natasha Gautam, MBBS, MS Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have appropriately responded to comments. Reviewers' comments: https://doi.org/10.1371/journal.pone.0326187.r003
Formally Accepted
Acceptance Letter - Natasha Gautam, Editor PONE-D-24-44578R1 PLOS ONE Dear Dr. Tokumo, 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: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Natasha Gautam Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0326187.r004

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