Diagnostic ability of confocal scanning ophthalmoscope for the detection of concurrent retinal disease in eyes with asteroid hyalosis

Su Hwan Park; Ji Hyoung Chey; Jun Heo; Kwang Eon Han; Sung Who Park; Iksoo Byon; Han Jo Kwon

doi:10.1371/journal.pone.0306091

Peer Review History

Original SubmissionDecember 12, 2023
25 Apr 2024 Decision Letter - Ogugua Ndubuisi Okonkwo, Editor PONE-D-23-38356Diagnostic Ability of Confocal Scanning Ophthalmoscope for the Detection of Concurrent Retinal Disease in Eyes with Asteroid HyalosisPLOS ONE Dear Dr. Kwon, 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. ==============================This research adds valuable information on the diagnosis of retina diseases in the presence of asteroid hylaosis and shows the superiority of TC-cSO imaging to the other imaging devices. The research is retrospective, but statistically analysis has been well conducted. I will suggest that the authors should include in the manuscript, why the specific statistical analysis was used and the merits of using them. Secondly, there is the issue of sample size which was raised by the reviewers. This should be addressed by the authors. Other minor issues pointed out below should also be addressed including making Table 4 clearer. ============================== Please submit your revised manuscript by Jun 09 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. 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). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Ogugua Ndubuisi Okonkwo, M.D. Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. 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 (if provided): Table 4 is not clear and requires more detail into how the numbers were derived. Please clarify this table for ease of understanding. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy 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 ****** 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 ****** 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 research is technically sound and the manuscript was written, results presented in an understandable manner. This research sought to find out the effectiveness and precision of the confocal scanning ophthalmoscope in identifying coexisting retinal diseases in eyes with asteroid hyalosis (AH). It compared the ultrawide-field (UWF) bicolor confocal scanning laser ophthalmoscope (BC-cSLO); true color confocal scanning ophthalmoscope (TC-cSO) and color fundus camera (CFC) to a reference diagnosis gotten during a dilated fundoscopy exam. TC-cSO was found to be able to diagnose coexisting retinal diseases with high accuracy and sensitivity in patients with AH. The strength of this study was the good interreader reliability (IRR).The weakness of the study is the small sample size and the limited range of scope of retinal diseases studied. In the 1st paragraph of the result section, it was stated that 100 eyes met the inclusion and exclusion criteria, of which 76 (76% ) of these eyes had concurrent retinal disease coexisting with asteroid hyalosis. However in table 1 the numbers beneath the sub heading "Concurrent Retinal Disease (Ne, %)" are not adding up, they seem to have exceeded 76 eyes, please clarify. Reviewer #2: It is a good study of retinal imaging through 3 devices in eyes with asteroid hyalosis (AH). UWF images with Optos and Eidon in eyes with AH are good 1. Can you explain any specific reason for the sample size of 100 eyes chosen? 2. How many individuals had both eyes asteroid hyalosis and how many had 1 eye alone with AH? if both eyes had AH- was 1 of the eyes chosen for the study? 3. ****** 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: Dr. Chineze Thelma Agweye 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.0306091.r001
Revision 1
28 May 2024 Author Response Dear Editor & Reviewers, We are very grateful to answer the comments about this manuscript provided by the editor and each of the reviewers. We appreciate all suggestions and corrections. All authors have carefully reviewed these comments. Our detailed responses to comments are addressed below. Academic Editor Comments This research adds valuable information on the diagnosis of retina diseases in the presence of asteroid hylaosis and shows the superiority of TC-cSO imaging to the other imaging devices. The research is retrospective, but statistically analysis has been well conducted. I will suggest that the authors should include in the manuscript, why the specific statistical analysis was used and the merits of using them. Secondly, there is the issue of sample size which was raised by the reviewers. This should be addressed by the authors. Other minor issues pointed out below should also be addressed including making Table 4 clearer. Response: The confusion matrix was employed for conducting specific analysis to evaluate diagnostic ability. The utilization of the confusion matrix for performance assessment offers several advantages. It provides a detailed breakdown of classification outcomes, including true positives, true negatives, false positives, and false negatives, enabling a deeper understanding of performance. Additionally, metrics derived from the confusion matrix such as accuracy, precision, sensitivity, and F1 score offer a comprehensive evaluation of the effectiveness across various classes or categories. In the Method section on page 8, we included the benefits of the analysis approach for comparing performance across individual devices, stated as follows: “Using the confusion matrix for performance evaluation offers detailed classification outcomes, while deriving key metrics like accuracy, precision, sensitivity, and F1 score provides a comprehensive evaluation of performance across different classes. Diagnostic and screening abilities for concurrent retinal diseases ~” The questions regarding the sample size of 100 eyes and the concurrent retinal disease of 76 eyes raised by Reviewer #1 and Reviewer #2, as well as the editor's comments on clarifying Table 4, have been addressed and revised below according to each comment section. Additional Editor Comments (if provided): Table 4 is not clear and requires more detail into how the numbers were derived. Please clarify this table for ease of understanding. Response: Thank you for valuable review. As you pointed out, to describe the numbers in the table, the manuscript and the legend of the table have been modified. Table 4 presents a comparison of diagnostic ability evaluation metrics derived from the confusion matrix to determine classification accuracy for three devices. Four ophthalmologists diagnosed six retinal diseases using fundus photographs of 100 eyes for three devices. The diagnostic performance was assessed by creating a confusion matrix for each device. The confusion matrix is composed of True Positive (TP), True Negative (TN), False Positive (FP), and False Negative (FN) values. In confusion matrix of Each disease, total number = TP + TN + FP + FN = 4 ophthalmologists × 100 eyes = 400 In confusion matrix of All diseases, total number = TP + TN + FP + FN = 4 ophthalmologists × 100 eyes × 6 diseases= 2,400 In the results section, the explanation of Table 4 has been modified as follows: "The four ophthalmologists diagnosed six concurrent retinal diseases using 100 fundus photographs for three imaging devices (CFC, BC-cSLO, and TC-cSLO), and the diagnostic performance of each imaging device was evaluated using confusion matrices. Table 4 summarizes the diagnostic capabilities of each imaging device." The legend of table 4 have been added to explain the numbers in the table as follows: “TP, TN, FP, and FN represent the values of the confusion matrix for each imaging device and disease. TP refers to the number of positive cases that were correctly identified. TN refers to the number of negative cases that were correctly identified. FP refers to the number of negative cases that were incorrectly identified as positive. FN refers to the number of positive cases that were incorrectly identified as negative. Accuracy (%) = (TP + TN) / (TP + TN + FP + FN) × 100 Sensitivity (%) = TP / (TP + FN) × 100 Specificity (%) = TN / (TN + FP) × 100 Precision (%) = TP / (TP + FP) × 100 F1 score = 2 × (Precision × Sensitivity) / (Precision + Sensitivity)” Additionally, I have moved the "All Diseases" column to the last position in Table 4 to prevent confusion with the six retinal diseases. Also, the Method section on page 8 provides a detailed explanation of how accuracy and sensitivity were calculated using the results from the confusion matrix. “Diagnostic and screening abilities for concurrent retinal diseases in patients with AH were investigated using the following four-step process: First, based on the medical records and three fundus images, the corresponding author diagnosed concurrent retinal disease for each retinal image as a reference diagnosis. The corresponding author created a list of potential retinal diseases including DR, dry and wet age-related macular degeneration (AMD), retinal vein occlusion (RVO), epiretinal membrane (ERM), and retinitis pigmentosa. Third, four independent ophthalmologists (S.H.P., J.H.C., J.H., and K.E.H.) recorded possible retinal diseases accompanying AH as diagnostic tests, based solely on fundus photographs taken with CFCs, UWF BC-cSLOs, and TC-cSOs. The diagnostic test was continued until each ophthalmologist interpreted all fundus photographs. Finally, the corresponding author compared the diagnoses of the four ophthalmologists against the reference diagnosis and constructed confusion matrices for each ophthalmologist's assessment. These matrices were aggregated to calculate the accuracy and sensitivity of each imaging device for each disease and to evaluate their diagnostic capabilities.” Reviewer #1: The research is technically sound and the manuscript was written, results presented in an understandable manner. This research sought to find out the effectiveness and precision of the confocal scanning ophthalmoscope in identifying coexisting retinal diseases in eyes with asteroid hyalosis (AH). It compared the ultrawide-field (UWF) bicolor confocal scanning laser ophthalmoscope (BC-cSLO); true color confocal scanning ophthalmoscope (TC-cSO) and color fundus camera (CFC) to a reference diagnosis gotten during a dilated fundoscopy exam. TC-cSO was found to be able to diagnose coexisting retinal diseases with high accuracy and sensitivity in patients with AH. The strength of this study was the good interreader reliability (IRR).The weakness of the study is the small sample size and the limited range of scope of retinal diseases studied. In the 1st paragraph of the result section, it was stated that 100 eyes met the inclusion and exclusion criteria, of which 76 (76% ) of these eyes had concurrent retinal disease coexisting with asteroid hyalosis. However in table 1 the numbers beneath the sub heading "Concurrent Retinal Disease (Ne, %)" are not adding up, they seem to have exceeded 76 eyes, please clarify. Response: Thank you for the correction. In Table 1, a correction has been made from RP 10 eyes to 3 eyes due to a typographical error, with no impact on other results in the paper. Consequently, Concurrent retinal disease is as follows: DR 20 eyes, Dry AMD 31 eyes, Wet AMD 9 eyes, RVO 6 eyes, ERM 33 eyes, and RP 3 eyes. Furthermore, when there are two or more retinal diseases present in eyes with DR, Dry AMD, Wet AMD, RVO, ERM, and RP, there are 22 eyes; when there are two retinal diseases, there are 18 eyes; and when there are three retinal diseases, there are 4 eyes. To avoid potential confusion arising from the discrepancy in the total count when labeling cases with two or more retinal diseases as "Multiple retinal diseases" in Table 1, we opted to differentiate between cases with two retinal diseases and those with three retinal diseases. Upon recalculating, if we add up all concurrent retinal diseases, including overlaps, the total number of individual cases would be 20 + 31 + 9 + 6 + 33 + 3 = 102 cases. To calculate the total number of eyes having concurrent retinal disease, we must subtract those overlaps (cases with multiple retinal diseases): 102 - (18 × 1) - (4 × 2) = 76 eyes. Therefore, the number is correct. Additionally, to aid comprehension, the following explanation has been added to the legend and footnote in Table 1: “Two retinal diseases and Three retinal diseases represent the number of eyes diagnosed with multiple diseases among the listed concurrent retinal disease (DR, Dry AMD, Wet AMD, RVO, ERM, and RP).” Reviewer #2: It is a good study of retinal imaging through 3 devices in eyes with asteroid hyalosis (AH). UWF images with Optos and Eidon in eyes with AH are good 1. Can you explain any specific reason for the sample size of 100 eyes chosen? Response: After excluding eyes with unsatisfactory fundus photography quality from a pool of 101 patients (119 eyes), the dataset was narrowed down to 89 patients (100 eyes). It's important to note that the selection was not deliberately targeted at 100 eyes; rather, the inclusion criterion led to 100 eyes being included in the analysis. The Method section on page 6 outlines the exclusion criteria as described below, along with an explanation in the flow diagram depicted in S1 Figure. “Patients with conditions other than AH that could affect the quality of fundus photography, such as corneal opacity, grade ≥4 nuclear opacity, or grade ≥2 posterior subcapsular opacity according to the Lens Opacities Classification System III, or vitreous hemorrhage were not included in the study. Additionally, patients with retinal or choroidal detachment that interfered with focusing on the entire macula, those whose pupils did not dilate to at least 4 mm under low light (5 lx), and those with involuntary eye movements causing overlapping images were excluded from the study.” 2. How many individuals had both eyes asteroid hyalosis and how many had 1 eye alone with AH? if both eyes had AH- was 1 of the eyes chosen for the study? Response: 89 patients (100 eyes) were included. 11 patients (12.4%) had bilateral involvement, while 78 patients (87.6%) had unilateral involvement. In Table 1, for the 89 patients included, the distribution is represented as Bilateral/Unilateral (Np, %) 11 (12.4%)/78 (87.6%). When AH is present in both eyes, fundus images from both eyes were included, rather than only fundus image from one eye. Attachments Attachment Submitted filename: Response to Reviewers AH_PlosOne 240523.docx https://doi.org/10.1371/journal.pone.0306091.r002
11 Jun 2024 Decision Letter - Ogugua Ndubuisi Okonkwo, Editor Diagnostic Ability of Confocal Scanning Ophthalmoscope for the Detection of Concurrent Retinal Disease in Eyes with Asteroid Hyalosis PONE-D-23-38356R1 Dear Dr. Kwon, 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, Ogugua Ndubuisi Okonkwo, M.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0306091.r003
Formally Accepted
25 Nov 2024 Acceptance Letter - Ogugua Ndubuisi Okonkwo, Editor PONE-D-23-38356R1 PLOS ONE Dear Dr. Kwon, 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. Ogugua Ndubuisi Okonkwo Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0306091.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .