Visual impairment in pseudoexfoliation from four tertiary centres in India

Aparna Rao; Niranjan Raj; Amiya Pradhan; Sirisha Senthil; Chandra S. Garudadri; P. V. K. S Verma; Prakriti Gupta

doi:10.1371/journal.pone.0233268

Peer Review History

Original SubmissionSeptember 16, 2019
18 Feb 2020 Decision Letter - Sanjoy Bhattacharya, Editor PONE-D-19-26019 Visual impairment in pseudoexfoliation from four tertiary centres in India PLOS ONE Dear Dr. Rao, 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. Two learned reviewers have provided extensive comments and criticisms. The manuscript could be revised incorporating commensurate changes that address all these comments and criticisms. We would appreciate receiving your revised manuscript by Apr 03 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Sanjoy Bhattacharya Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 1. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. 2) In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) the recruitment date range (month and year), b) a description of any inclusion/exclusion criteria that were applied to participant recruitment, c) a statement as to whether your sample can be considered representative of a larger population and d) a description of how participants were recruited. 3) Please provide a sample size and power calculation in the Methods, or discuss the reasons for not performing one before study initiation. " 4. Thank you for including your ethics statement: Institutional review board of LV Prasad eye institute, MTC campus, Bhubaneswar IEC number: 2016-12-CB-12 Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”). For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research. 5. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data. 6. Thank you for stating in your Funding Statement: This work was partly funded by the Wellcome Trust/DBT India Alliance grant: ref no IA/CPHI/15/1/502031 awarded to Aparna Rao. Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf [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: Partly Reviewer #4: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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: No Reviewer #4: 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 Reviewer #4: No ****** 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: This Research Article designed Prospectively to analyse the disease burden of pseudoexfoliation stages and the data are supportive, Statistical Analysis performed appropriately, All datas underlying the findings are available, The manuscript is written in standard English. Reviewer #2: the only thing I recommend is to add a definition of pseudo exfoliation to the article. the article was written in a very good way, understandable language, clear, and no typo in this article. also the tables were well organized and easy to understand by the reader. Reviewer #3: I read with interest the article entitled .: "Visual impairment in pseudoexfoliation from four tertiary centers in India" by Aparna Rao al., Regarding pseudoexfoliation (PXF) disease stages from East and South India. This research concerns a large number of individuals (over 6.ooo patients). I found it very difficult to read this article because I didn't like it. From an epidemiological point of view this syndrome first discovered in the Scandinavian countries is now considered ubiquitous. The authors state that it is not known why this glaucoma comes. Actually, the furfuraceous material that can be found in any organ indicates a serious alteration of the metabolism of the tissues involved. High pressure glaucoma consists from a molecular point of view in pro-apoptotic signals that reach the head of the optic nerve and induce the death of ganglion cells. Therefore, trabecular meshwork is the first tissue to be involved (see Saccà et al. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma. Aging Res Rev. 2016; 29: 26-41) and trabecular dandruff there suggests that this structure is seriously damaged and therefore unable to fulfill its barrier functions (Saccà et al. The Outflow Pathway: A Tissue With Morphological and Functional Unity. J Cell Physiol. 2016; 231: 1876-93), hence the increase in intraocular pressure and glaucoma. Even the diagnosis of pseudoexfoliative glaucoma may not be so simple, indeed, according to the only macroscopic presence of the dandruff is uncertain. This syndrome acts like multiple sclerosis. Depending on the affected tissue, the nosological entity of the disease manifests itself: if the iris is affected, iris atrophic changes occur if the lens is affected, the cataract occurs, if the zonula is affected, lens dislocation occurs, if the trabecular meshwork is affected, have glaucoma. Reviewer #4: Although in general the manuscript is presented in an intelligible fashion, there are some errors in the use and structure of the English language which make it hard to follow at some points. Proofreading and better use of the english language should be highly considered. Some of them are highlighted in the comments. methods in abstract, Line 37: clinical "and" demographic details instead of clinical, demographic should be used Line 87: missing the word "primary" before angle closure glaucoma (PACG) Line 88: focus instead of focuses should be used Line 111: "electronic media record database": do the authors mean media or medical? Line 111-116: sentence is hard to follow. medications is written twice. Line 123: Does "pattern of deposits, diagnosis, ocular associations and number of medications at baseline" refer to data collected from referrals outside? It is not clear to the reader. Line 137: "open or closed angles on gonioscopy, radial" missing the word "and" before radial Line 143: Missing the word pseudoexfoliation before glaucoma Line 161: "anti-glaucoma educations". educations should be replaced by the appropriate word Line 162: "(for totally bind asymptomatic eyes)"bind should be replaced by the appropriate word Line 184: "proportions among al patients"al should be replaced by the appropriate word Line 185: "Since the diagnosis or severity of PXF in one eye has no proven correlation to the risk /condition of the other eye", However the authors should consider that there is a variable but increased probability of developing Pseudoexfoliation in the unaffected eye Line 191: locations instead of location Line 198: add "the" before rest Line 210" authors should include if this finding was statistically significant Line 212: add "being" before significantly Line 217: missing word after medical/surgical Line 220: "were" should be replaced with "was" Line 226: abbreviation AGM was not explained Line 256: The authors mention that anterior and posterior segment pathologies were noted and analyzed. However it is not clear If they stratified for these pathologies as they could significantly impact visual acuity apart from the glaucomatous changes. Line 366: removed one of the two "with" Line 508:SD was not included in the list with abbreviations Figure 1 does not show up properly. Please review. Figure 2 seems blurry. ****** 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: Yes: NAYEF K ALSHAMMARI Reviewer #2: Yes: Feras Mohder Reviewer #3: Yes: Sergio C. Saccà Reviewer #4: 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 be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0233268.r001
Revision 1
22 Mar 2020 Author Response • PONE-D-19-26019 Visual impairment in pseudoexfoliation from four tertiary centres in India PLOS ONE Dear Dr. Rao, 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. Two learned reviewers have provided extensive comments and criticisms. The manuscript could be revised incorporating commensurate changes that address all these comments and criticisms. We would appreciate receiving your revised manuscript by Apr 03 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Sanjoy Bhattacharya Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 1. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. Answer1: We have made suggested corrections and additions in the text and submission regarding ethics statement, Page 6. 2) In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) the recruitment date range (month and year), b) a description of any inclusion/exclusion criteria that were applied to participant recruitment, c) a statement as to whether your sample can be considered representative of a larger population and d) a description of how participants were recruited. Answer: We have now added and expanded the recruitment details of the participants of the study which includes the recruitment date or representative sample details, Page 6. The inclusion/exclusion criteria have already been detailed elaborately in the text in the section clinical definition and stratification, page 7, which has been maintained and elaborated, as suggested by the reviewer. 3) Please provide a sample size and power calculation in the Methods, or discuss the reasons for not performing one before study initiation. " Answer3: We have now included a sample size calculation in the methods/statistics section, page 9. 4. Thank you for including your ethics statement: Institutional review board of LV Prasad eye institute, MTC campus, Bhubaneswar IEC number: 2016-12-CB-12 Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”). For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research. Answer 4: The ethics statement has been added, as suggested, Page 6. 5. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data. Answer 5: Additional data has been provided as a separate attachment now 6. Thank you for stating in your Funding Statement: This work was partly funded by the Wellcome Trust/DBT India Alliance grant: ref no IA/CPHI/15/1/502031 awarded to Aparna Rao. Please provide an amended statement that declares all the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement. Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf Answer 6: The funding statement has been amended, as suggested. 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: Partly Reviewer #4: Yes ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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: No Reviewer #4: 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 Reviewer #4: No ________________________________________ 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: This Research Article designed Prospectively to analyse the disease burden of pseudoexfoliation stages and the data are supportive, Statistical Analysis performed appropriately, All datas underlying the findings are available, The manuscript is written in standard English. Answer1: We thank the reviewer for the positive comments which encourage us to explore further into pseudoexfoliation which is a baffling disease entity. We are encouraged also to keep up the aulity of our work to meet expectations of the reviewers in the future too. Reviewer #2: the only thing I recommend is to add a definition of pseudo exfoliation to the article. the article was written in a very good way, understandable language, clear, and no typo in this article. also the tables were well organized and easy to understand by the reader. Answer 2: We than the reviewer for this suggestion which has been added, as suggested. Reviewer #3: I read with interest the article entitled .: "Visual impairment in pseudoexfoliation from four tertiary centers in India" by Aparna Rao al., Regarding pseudoexfoliation (PXF) disease stages from East and South India. This research concerns a large number of individuals (over 6.ooo patients). I found it very difficult to read this article because I didn't like it. From an epidemiological point of view this syndrome first discovered in the Scandinavian countries is now considered ubiquitous. The authors state that it is not known why this glaucoma comes. Actually, the furfuraceous material that can be found in any organ indicates a serious alteration of the metabolism of the tissues involved. High pressure glaucoma consists from a molecular point of view in pro-apoptotic signals that reach the head of the optic nerve and induce the 1death of ganglion cells. Therefore, trabecular meshwork is the first tissue to be involved (see Saccà et al. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma. Aging Res Rev. 2016; 29: 26-41) and trabecular dandruff there suggests that this structure is seriously damaged and therefore unable to fulfill its barrier functions (Saccà et al. The Outflow Pathway: A Tissue With Morphological and Functional Unity. J Cell Physiol. 2016; 231: 1876-93), hence the increase in intraocular pressure and glaucoma. Even the diagnosis of pseudoexfoliative glaucoma may not be so simple, indeed, according to the only macroscopic presence of the dandruff is uncertain. This syndrome acts like multiple sclerosis. Depending on the affected tissue, the nosological entity of the disease manifests itself: if the iris is affected, iris atrophic changes occur if the lens is affected, the cataract occurs, if the zonula is affected, lens dislocation occurs, if the trabecular meshwork is affected, have glaucoma. Answer 3: We agree with the reviewer’s pertinent views regarding possible mechanisms of tissues getting affected with the exfoliative material. The disease is ubiquitous as pointed out however this occurs with varied prevalance rates across the globe. This topic of glaucoma in PXF is indeed a complex issue which has baffled many scientist and has eluded a clear description of events leading to glaucoma. Yet, it is known that presence of exfoliative material by itself does not mean functional disturbances which is reported in studies showing no correlation of extent of exfoliative deposits in eye with presence of glaucoma (Cobb J et al- Br J Ophthalmol 2004; 88:1002-1003) If material causes mechanical blockage of TM pores with the deposits in all eyes, glaucoma would be seen in all eyes with PXF which is rarely seen in clinical practice. While it is known that these may cause local functional disturbances in the tissues including the TM, the mechanism by which that happens and what triggers the disturbance in some eyes at specific time points only is unknown. This is exactly the reason why all eyes with PXF do not end up with glaucoma even in the same patient with bilateral disease. The molecular events triggering the functional tissue damage is also largely unclear which is discussed in the review article (reference 1). Similar perplexing issues of the disease are discussed in the Journal of glaucoma supplement 1, Volume 27, 2018 discussing several perplexing issues on this disease .Our own lab is working at unraveling the disturbances in eyes with PXF and those without PXG at a molecular level. We also are aware of TM functional damage and cell death in glaucoma in general but would like to clarify that it is not only apoptosis that causes cell death in the human TM in glaucoma. My PhD thesis study evaluating cellular mechanisms of cell death in TM (which largely involved insights from Dr Sacca’s work an articles) found specific molecular events being triggered at specific severity of tissue damage which is not restricted to apoptotic signals only and rather involved a down-regulation of apoptotic molecules contrary to traditional wisdom (paper under review). We are also studying how TM in PXG eyes are affected and are working on an in vitro-model of the same. While several others are also working on the questions the reviewer has suggested and alluded above, we still believe that the glaucoma pathogenesis in PXF remains a mystery. This is the reason why we clinicians cannot predict which eyes are at risk of developing glaucoma and also fall short in predicting when the onset of glaucoma/or tissue damage can occur in any eye. We would be delighted to share our preliminary results with the reviewer when experiments complete regarding the above points of TM damage in PXF and we would be happy to get further insights from the reviewer on this topic. Reviewer #4: Although in general the manuscript is presented in an intelligible fashion, there are some errors in the use and structure of the English language which make it hard to follow at some points. Proofreading and better use of the english language should be highly considered. Some of them are highlighted in the comments. methods in abstract, Line 37: clinical "and" demographic details instead of clinical, demographic should be used Line 87: missing the word "primary" before angle closure glaucoma (PACG) Line 88: focus instead of focuses should be used Line 111: "electronic media record database": do the authors mean media or medical? Line 111-116: sentence is hard to follow. medications is written twice. Line 123: Does "pattern of deposits, diagnosis, ocular associations and number of medications at baseline" refer to data collected from referrals outside? It is not clear to the reader. Line 137: "open or closed angles on gonioscopy, radial" missing the word "and" before radial Line 143: Missing the word pseudoexfoliation before glaucoma Line 161: "anti-glaucoma educations". educations should be replaced by the appropriate word Line 162: "(for totally bind asymptomatic eyes)"bind should be replaced by the appropriate word Line 184: "proportions among al patients"al should be replaced by the appropriate word Line 185: "Since the diagnosis or severity of PXF in one eye has no proven correlation to the risk /condition of the other eye", However the authors should consider that there is a variable but increased probability of developing Pseudoexfoliation in the unaffected eye Line 191: locations instead of location Line 198: add "the" before rest Line 210" authors should include if this finding was statistically significant Line 212: add "being" before significantly Line 217: missing word after medical/surgical Line 220: "were" should be replaced with "was" Line 226: abbreviation AGM was not explained Line 256: The authors mention that anterior and posterior segment pathologies were noted and analyzed. However it is not clear If they stratified for these pathologies as they could significantly impact visual acuity apart from the glaucomatous changes. Line 366: removed one of the two "with" Line 508:SD was not included in the list with abbreviations Figure 1 does not show up properly. Please review. Figure 2 seems blurry. Answer: We than the reviewer for such an exhaustive review and correction at appropriate places. The text has been edited for grammar and typos. All detailed corrections given above have been incorporated, as suggested. The resolution of figures has also been improved, as suggested. Attachments Attachment Submitted filename: Plosone comments.docx https://doi.org/10.1371/journal.pone.0233268.r002
4 May 2020 Decision Letter - Sanjoy Bhattacharya, Editor Visual impairment in pseudoexfoliation from four tertiary centres in India PONE-D-19-26019R1 Dear Dr. Rao, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Sanjoy Bhattacharya 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 #1: All comments have been addressed Reviewer #4: 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 #1: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #4: 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 #1: Yes Reviewer #4: 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 #1: Yes Reviewer #4: 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 #1: This Research Article designed Prospectively to analyse the disease burden of pseudoexfoliation stages and the data are supportive, Statistical Analysis performed appropriately, All datas underlying the findings are available, The manuscript is written in standard English. Reviewer #4: (No Response) ****** 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 #1: Yes: NAYEF K ALSHAMMARI Reviewer #4: No https://doi.org/10.1371/journal.pone.0233268.r003
Formally Accepted
18 May 2020 Acceptance Letter - Sanjoy Bhattacharya, Editor PONE-D-19-26019R1 Visual impairment in pseudoexfoliation from four tertiary centres in India Dear Dr. Rao: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Sanjoy Bhattacharya Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0233268.r004

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