Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis

Jiajia Yao; Wanli Huang; Lixia Gao; Yan Liu; Qi Zhang; Juncai He; Li Zhang

doi:10.1371/journal.pone.0304283

Peer Review History

Original SubmissionNovember 21, 2023
6 Feb 2024 Decision Letter - Tatsuya Inoue, Editor PONE-D-23-36631Comparative efficacy of Anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: a network meta-analysisPLOS ONE Dear Dr. Zhang, 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 Mar 22 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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Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 3. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: 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: In this Meta-Analysis study, the authors rationally picked up some previous clinical studies investigating visual and morphological prognosis after anti-VEGF therapy according to morphological patterns, and then concluded DRT had the highest increase in BCVA, while SRD showed largest reduction of CMT. Generally, the significance of this study is high, and discussion about pathogenesis of each DME pattern is interesting. One noted matter is that the authors overemphasized about the superiority of conbercept in abstract and discussion. In this review, comparative efficacies among each drug were not focused, thus description about each drug should be omitted, especially last paragraph in this manuscript. Reviewer #2: In this study, the authors evaluated the comparative efficacy for the anti-VEGF therapy in DME with different OCT patterns. I consider this paper to be an interesting analysis of a vast amount of data, but with a number of major flaws. 1. Introduction: The authors cite a paper by Seo et al (2016). that classifies DME into three patterns. However, the 20 papers analyzed by the authors include meta-analysis of papers published before 2016, but are those cases correctly classified into the three categories? If the authors evaluate the treatment effect for each DME pattern according to the classification based on the Seo et al. paper, I believe that the meta-analysis should be limited to papers classified after 2016 according to the Seo et al. paper. 2. Results: As the authors stated, this study was not able to match the baseline visual acuity or CMT of each group. However, we need to know their baseline visual acuity and CMT values as reference values and should indicate them in the paper. 3. What are the anti-VEGF treatment regimens and the treatment and follow-up periods of the studies included in this meta-analysis? If these are different, the comparisons will be very meaningless. ****** 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: 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.] 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. https://doi.org/10.1371/journal.pone.0304283.r001
Revision 1
20 Mar 2024 Author Response Reviewer #1: In this Meta-Analysis study, the authors rationally picked up some previous clinical studies investigating visual and morphological prognosis after anti-VEGF therapy according to morphological patterns, and then concluded DRT had the highest increase in BCVA, while SRD showed largest reduction of CMT. Generally, the significance of this study is high, and discussion about pathogenesis of each DME pattern is interesting. One noted matter is that the authors overemphasized about the superiority of conbercept in abstract and discussion. In this review, comparative efficacies among each drug were not focused, thus description about each drug should be omitted, especially last paragraph in this manuscript. Reply 1: Thank you very much for your comments and suggestions. In this review, we have only compared the variation in the effectiveness outcomes between anti-VEGF drugs for the patients with DRT (Supplemental Figure 3), CME (Supplemental Figure 4), and SRD (Supplemental Figure 5) respectively. As you mentioned, our results found that conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups, which was not able to provide enough evidence to support the superiority of conbercept in the treatment of DME. The comparative efficacies of each drug need more analysis in the future research. Thus, we have changed some sentences in this manuscript. Your comments made our conclusions more precise. Reviewer #2: In this study, the authors evaluated the comparative efficacy for the anti-VEGF therapy in DME with different OCT patterns. I consider this paper to be an interesting analysis of a vast amount of data, but with a number of major flaws. 1. Introduction: The authors cite a paper by Seo et al (2016). that classifies DME into three patterns. However, the 20 papers analyzed by the authors include meta-analysis of papers published before 2016, but are those cases correctly classified into the three categories? If the authors evaluate the treatment effect for each DME pattern according to the classification based on the Seo et al. paper, I believe that the meta-analysis should be limited to papers classified after 2016 according to the Seo et al. paper. Reply: Thank you very much for your comments and suggestions. The paper by Seo et al (2016). that classifies DME into three patterns according to the paper by Otani, T. et al (1999). The 20 papers analyzed in this meta-analysis were published after 1999. Thus, we have replaced the paper by Otani, T. et al (1999) as the reference in our revised manuscript according to your suggestion. 2. Results: As the authors stated, this study was not able to match the baseline visual acuity or CMT of each group. However, we need to know their baseline visual acuity and CMT values as reference values and should indicate them in the paper. Reply: Thank you very much for your comments and suggestions. We have added the baseline value for BCVA or CMT of each group in Supplemental Figure 1 and in Supplemental Table 2 in our revised manuscript according to your suggestion. Your suggestion made our manuscript more professional. 3. What are the anti-VEGF treatment regimens and the treatment and follow-up periods of the studies included in this meta-analysis? If these are different, the comparisons will be very meaningless. Reply: Thank you for your insightful question regarding the variability in anti-VEGF treatment regimens and the treatment and follow-up periods of the studies included in our meta-analysis. We recognize your concern that the inconsistency in these parameters could potentially affect the comparability of study outcomes. In response to this, we have meticulously detailed the follow-up duration, average number of injections, and medication dosage for all studies included in our meta-analysis in Supplemental Table 2. This comprehensive listing serves to present the basis for our analysis transparently. Following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions1, we conducted an extensive meta-regression analysis to examine the impact of these variables on two critical outcomes: Best Corrected Visual Acuity (BCVA) and Central Macular Thickness (CMT) across different patient groups (DRT, CME, and SRD). Our findings, outlined in Supplemental Table 3, reveal that the variations in follow-up time, average number of injections, and medication dosage do not significantly influence the outcomes of BCVA and CMT across the six patient groups examined. This detailed analysis underscores that, despite the clinical and methodological diversity among the included studies, the differences in treatment regimens and follow-up periods do not significantly alter the effects on BCVA and CMT outcomes. Such results are crucial in affirming the validity of our meta-analysis, suggesting that the differences in treatment specifics and follow-up durations observed across studies do not detract from our ability to derive meaningful conclusions from the aggregated data. Therefore, while acknowledging the inherent heterogeneity in the studies we reviewed, our meta-regression analysis provides empirical evidence that this variability does not significantly impact the key outcomes of interest. This reinforces our belief that the results of our meta-analysis offer valuable insights into the effects of anti-VEGF treatments, despite the variability in treatment details and follow-up periods among the included studies. We hope this comprehensive explanation, supported by the detailed enumeration in Supplemental Table 2 and backed by statistical analysis, adequately addresses your concerns. We are grateful for your thorough review and appreciate the opportunity to clarify this aspect of our research further. Additionally, we have included the meta-regression analysis details in the results and supplementary materials for your reference. Reference：1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated August 2023). Cochrane, 2023. Available from www.training.cochrane.org/handbook. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0304283.r002
9 May 2024 Decision Letter - Tatsuya Inoue, Editor Comparative efficacy of Anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: a network meta-analysis PONE-D-23-36631R1 Dear Dr. Zhang, 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, Tatsuya Inoue Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #2: 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: The authors have added details of the meta-regression analysis in the results and supplementary materials, and I believe they have adequately responded to my comments. ****** 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 #2: No ******** https://doi.org/10.1371/journal.pone.0304283.r003
Formally Accepted
15 May 2024 Acceptance Letter - Tatsuya Inoue, Editor PONE-D-23-36631R1 PLOS ONE Dear Dr. Zhang, 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. Tatsuya Inoue Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0304283.r004

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