Collagen imaging reveals synergistic effects of sutures and host-donor misalignment on topographical irregularities in penetrating keratoplasty

Himanshu Gururani; Sai Naga Sri Harsha Chittajallu; Minal Doulatramani; Viswanath Chinthapenta; Sayan Basu; Ramji M.

doi:10.1371/journal.pone.0308204

Peer Review History

Original SubmissionMarch 11, 2024
11 Mar 2024 Author Response Attachments Attachment Submitted filename: Response to Reviewers_Revision 3.docx https://doi.org/10.1371/journal.pone.0308204.r001
16 Jun 2024 Decision Letter - Bhavana Sharma, Editor PONE-D-24-09388Collagen imaging reveals synergistic effects of sutures and host-donor misalignment on topographical irregularities in penetrating keratoplastyPLOS ONE Dear Dr. M, 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 Jul 31 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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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. Thank you for stating the following financial disclosure: [This study was funded by the intramural funds of LV Prasad Eye Institute (LVPEI), Hyderabad; and partially sup- ported under Prime Minister Doctoral Research Fellowship grant (to author HG) by the Department of Science and Technology, India, Sci- ence, and Engineering Research Board, India, Confederation of Indian Industries, India, the Government of India & LVPEI.]. 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."" If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 3. 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: Please include the following as a limitation of study : the PK procedure was spread over two days, and then the birefringence data was taken for all the corneas which can potentially affect the measurements , due to changes in mechanical strength and integrity . Further please address the concerns of referees . [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: Yes Reviewer #2: Yes Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: I Don't Know Reviewer #3: Yes ****** 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: Yes Reviewer #2: Yes Reviewer #3: 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: The study is well conceived, performed rigorously and the manuscript describes it lucidly. The introduction mentions DALK and FLAK as techniques that potentially minimize astigmatism compared to PK. This is not supported by evidence, and may be omitted. Topography guided selective suture removal is generally a post operative procedure, and may be removed from intraoperative measures to reduce astigmatism. Reviewer #2: Changes suggestions after Line 66: Original: [13,14]. Further, the techniques such as SSR, sequential suture removal [15,16], intra-stromal ring (ICRS) insertion [17], intraocular lens (IOLs) [18,19], Photorefractive Keratectomy [20,21],laser in-situ keratomileusis (LASIK) [22,23] and repeat keratoplasty [24] are used post-operatively to manage PPKA. Suggestion: [13,14]. Further, the techniques such as sequential suture removal (SSR) [15,16], insertion of intra corneal ring segments (ICRS) [17], intraocular lens (IOLs) [18,19], Photorefractive Keratectomy (PRK) [20,21],laser in-situ keratomileusis (LASIK) [22,23] and repeat keratoplasty [24] are used post-operatively to manage PPKA. Reviewer #3: Query 1: The authors have selected five corneas for the experiment. Kindly provide more details about the criteria for tissue selection. It is mentioned that corneas with an endothelial cell count (ECC) of less than 2500 were selected. Were there any additional criteria for selection, such as a lower limit for ECC, corneal thickness, or the presence of stromal folds? Additionally, were any tests performed to assess the biomechanical properties of the selected corneal tissues? Query 2: The absence of topographical data for the tissues makes it challenging to determine whether the change in orientation of the graft had any effect on the final birefringence pattern or apposition. ****** 6. 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: Yes: Frederico Bicalho Dias da Silva Reviewer #3: Yes: Sonam Yangzes ******** [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. Attachments Attachment Submitted filename: Changes suggestions.docx https://doi.org/10.1371/journal.pone.0308204.r002
Revision 1
1 Jul 2024 Author Response Response to Editor (Reviewer comments are shown in black-colored text, and responses to reviewer comments are shown in blue-colored text) Editor: (1) Please include the following as a limitation of study: the PK procedure was spread over two days, and then the birefringence data was taken for all the corneas which can potentially affect the measurements, due to changes in mechanical strength and integrity. i. As suggested by the editor, the authors have incorporated the changes in the revised manuscript. ii. The changes are reflected in lines 454-456, p21. Response to Reviewer-1 (Reviewer comments are shown in black-colored text, and responses to reviewer comments are shown in blue-colored text) Reviewer #1: The study is well conceived, performed rigorously and the manuscript describes it lucidly. The introduction mentions DALK and FLAK as techniques that potentially minimize astigmatism compared to PK. This is not supported by evidence, and may be omitted. Topography guided selective suture removal is generally a post operative procedure, and may be removed from intraoperative measures to reduce astigmatism. i. The authors thank the reviewer for the appreciating the rigor that was put into the manuscript and the work conducted by the authors. ii. Based on the reviewer’s suggestions, the authors have omitted the DALK and the FLAK from the introduction section. iii. The authors agree with the reviewer that topography guided selective suture removal is used post operatively and therefore has been removed from the intraoperative measures. iv. As per the reviewer’s suggestion, the above points have been incorporated in the revised manuscript, lines 59-67, see p 3. Response to Reviewer-2 (Reviewer comments are shown in black-colored text, and responses to reviewer comments are shown in blue-colored text) Reviewer #2: Changes suggestions after Line 66: Original: [13,14]. Further, the techniques such as SSR, sequential suture removal [15,16], intra-stromal ring (ICRS) insertion [17], intraocular lens (IOLs) [18,19], Photorefractive Keratectomy [20,21],laser in-situ keratomileusis (LASIK) [22,23] and repeat keratoplasty [24] are used post-operatively to manage PPKA. Suggestion: [13,14]. Further, the techniques such as sequential suture removal (SSR) [15,16], insertion of intra corneal ring segments (ICRS) [17], intraocular lens (IOLs) [18,19], Photorefractive Keratectomy (PRK) [20,21],laser in-situ keratomileusis (LASIK) [22,23] and repeat keratoplasty [24] are used post-operatively to manage PPKA. i. As per the reviewer’s suggestion, the above changes have been incorporated in the revised manuscript, lines 67-70, see p 3-4. Response to Reviewer-3 (Reviewer comments are shown in black-colored text, and responses to reviewer comments are shown in blue-colored text) Reviewer #3: Query 1: The authors have selected five corneas for the experiment. Kindly provide more details about the criteria for tissue selection. It is mentioned that corneas with an endothelial cell count (ECC) of less than 2500 were selected. Were there any additional criteria for selection, such as a lower limit for ECC, corneal thickness, or the presence of stromal folds? Additionally, were any tests performed to assess the biomechanical properties of the selected corneal tissues? i. The inclusion criterion for the corneas were endothelial cell density of less than 2500. There was no lower limit for the cell density. However, the optical quality of the corneas was assessed for the presence of excessive number of stromal folds and tissue swelling. Based on these inspections, the corneas were included in the study. ii. The authors would like to clarify that no additional tests were performed to assess the biomechanical properties of the cornea. However, as mentioned in the manuscript (see p7, line 149-154), the central distance between isotropic points (IPs; zones of zero birefringence, refer to our previous work (4-6 mm) was also chosen as inclusion criteria to ensure the similarity in birefringence across all the tested corneas. iii. The authors have incorporated the details related to inclusion criterion in the revised manuscript, see p7, lines 150-153. Reviewer #3: Query 2: The absence of topographical data for the tissues makes it challenging to determine whether the change in orientation of the graft had any effect on the final birefringence pattern or apposition. i. The authors agree with the reviewer that the absence of the topographic data makes it challenging to ascertain that the change in the graft’s orientation affects the final birefringence pattern. It is typically expected that the reorientation of the graft would topographically alter its position, and a 30-degree misalignment would result in a 30-degree change in the angular position of isotropic points on the corneal surface. ii. However, the authors would like to emphasize that the peculiar change in the disposition of the IPs (Ex.: -64-degree change for 30-degree mismatch) over the corneal surface indirectly suggests the influence of structural mismatch between the graft and the host tissue on the overall topographic irregularity, as the disposition of the IPs depends on both curvature and stress distribution in the cornea. iii. Based on the present findings, the authors suggest that the topographic irregularity observed in PK corneas seems to be a coupled phenomenon involving an interplay of suture tension and structural misalignment between the graft and the donor. iv. The authors believe that multiple experimental studies with large human cornea samples are necessary to establish detailed insights on the implications of structural aspects of the cornea on astigmatism in both pre- and post-surgical scenarios. Nevertheless, the results of the present study support the importance of structural matching between the host and the donor cornea during PK. v. Additionally, structural marking could be introduced as an additional step in eye banking protocols, which would involve marking the harvested cornea in nasal-temporal and superior-inferior directions to facilitate the structural matching of the graft with the donor's eye by the surgeons. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0308204.r003
19 Jul 2024 Decision Letter - Bhavana Sharma, Editor Collagen imaging reveals synergistic effects of sutures and host-donor misalignment on topographical irregularities in penetrating keratoplasty PONE-D-24-09388R1 Dear Dr. Ramji M 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, Bhavana Sharma, MS Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0308204.r004
Formally Accepted
29 Jul 2024 Acceptance Letter - Bhavana Sharma, Editor PONE-D-24-09388R1 PLOS ONE Dear Dr. M., 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. Bhavana Sharma Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0308204.r005

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