PONE-D-23-27405Comparison of Foraging Interactive D-prime and Angular Indication Measurement Stereoacuity with different methods to assess stereopsisPLOS ONE

Dear Dr. Neupane,

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.

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ACADEMIC EDITOR:  Both the reviewers have expressed concerns and provided some useful suggestions. Please address the comments thoroughly.

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Amithavikram R Hathibelagal, Ph.D.

Academic Editor

PLOS ONE

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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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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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: No

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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

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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: General Comments:

The study introduces two novel stereo measurement techniques, AIM and FlnD, and compares them with established tests such as 2AFC, Randot, and Titmus fly test. While the manuscript is technically sound, there needs a major restructuring with clarification and refinement for several points.

Clarity of Stimuli: The description of the FlnD noise stimulus needs further clarification. The term "noise" typically implies random dots without any signal. Consider renaming the target or providing a clear description of what subjects saw and responded to.

Viewing Distance: Ensure that details about the self-administrable tests, such as FlnD, AIM, and 2AFC, include information on how the viewing distance was maintained at 80 cm. Inconsistencies in viewing distance could contribute to data variation.

Aim of the study: Lines 137-144 outline the aims of the study but could be clarified. The lines starts out to stating there are 2 aims and explaining 5 aims. Consider explaining the features of FlnD and AIM in the introduction and focusing on the aims and objectives in this section.

Sections Organization: It is highly recommended that the FlnD and AIM results be combined as a single experiment for better coherence. The readers will be more interested in learning about the two paradigms rather than learning how the AIM came into being and to solve which problems of the FlnD paradigm. The author can discuss why AIM performed better than FlnD at the stereo thresholding in the discussion section.

Stats: Using stats to compare the results between the normal and binocular impaired individuals will lead to false results due to the huge uneven sample size

Specific Line-by-Line Comments:

Line 52: The classic sign for macular degeneration includes macular atrophy, drusens etc and the impact of these is loss of stereopsis. Stating stereopsis as a biomarker for degenerative diseases will be an error.

Line 115: Recheck the reference for the loss of stereoacuity due to refractive error and amblyopia as it refers to a paper related to retinal eccentricity.

Line 195-196: Provide consistency in units for the lower and upper bound min and max disparity, considering reporting in degrees.

Line 200-204: Clarify how the targets for the ring and noise stimuli were shifted towards opposite side and yet one produces crossed and another produces uncrossed disparities.

Line 275-276: Complete the sentence “Matlab’s anovan and multcompare functions for ANOVA and planned comparisons between tests”.

Line 290: Address the distribution of data in the statistical analysis section (if the data is normally distributed). Also, 2-way ANOVA was performed but looking at the fig 3, FlnD data, the mean and median are quite apart from each other.

Line 299: Clarify that whiskers usually represent 1st and 99th percentiles, not outliers.

Line 306: Explain the rationale for excluding values >3000 arcsec from analysis. Specially when they belong to the binocular impaired group, one would expect the stereo to be quite poor. If the data is skewed because of those subjects, a possibility would be to renumber stereo thresholds >3000 as 3000 and mention the reason for 3000 arcsec as the cutoff

Line 310-312: Discuss the potential implications of the observed variability

Line 314: p-value can never be exactly 0.

Line 345: “purple dot” – please keep colours consistent

Line 347: “Each figure contains 1 data point for each participant for Randot” shouldn’t the total number of dots be 20?

Line 406: Provide reasons for not including 2AFC in the comparison; consider combining the first and second experiments.

Line 457:Clarify the unit "5 X 1.25."

Line 457: It will be advisable to look at the learning in 2AFC and FlnD?

Line 489-499: Avoid repetition of introduction points and directly transition to conclusion statements.

Line 514: AIM was not tested on amblyopes in this manuscript.

Comments on the Figures:

Fig 3:

The different colours for the 6 tests are not required.

The horizontal jittering in 2AFC and clinical test seems to be huge. Please maintain uniform jittering.

Figure 4:

The normal can be given a single colour while the binocular impaired can be assigned a different colour and kept that uniform with figure 3. Also, number of subjects are not consistent.

Figure 5:

Consider combining with Figure 4 as panel E for easier comparison.

Figure 6:

Unequal number of subjects are presented here.

The graphs are repeated, for example randot Vs Titmus fly, or Titmus fly vs Randot will be same. Consider keeping only one to avoid confusion.

What additional inferences does the histogram generate?

Are these data points average of the 4 spatial frequency?

Consider including the Rsq value

Figure 7:

Align captions above the graphs for clarity.

Figure 11: Please remove repetitions of the graphs and mention the R sq and p values.

Reviewer #2: The study reports the inter-technique comparison and intra-technique repeatability of two new psychophysical measures of stereoacuity, relative to conventional clinical techniques and 2AFC psychophysical techniques. The two new tests were themselves quite repeatable but there was very little agreement between the various tests of stereoacuity. The time taken for the two new tests were shorter than conventional 2AFC techniques but significantly longer than the clinical tests of stereoacuity. These results are discussed in the context of a speed-accuracy trade-off in the assessment of stereoacuity.

The manuscript is easy to read and more or less free of grammatical errors. There are some confusing sentences dispersed all through the manuscript (indicated below in the specific comments) that need to be fixed. The figures are all of very low resolution and the details were not visible upon magnification. This needs to be fixed as well. In addition to these issues, the following issues need to be addressed in the manuscript.

1. While I do not have any concern with the quality of the science pursued in this manuscript, I worry about the utility of these techniques in the future assessment of stereoacuity in the clinic/research settings. This concern is more for the clinical application, and it primarily stems from the time it takes to complete the test, vis-à-vis, the present techniques of Titmus or RanDot stereoacuity. I appreciate that the two new techniques are far more scientifically rigorous, and they overcome several limitations fraught with the present testing paradigms. However, is this a motivation enough for an average clinician to switch over to this technique? These techniques take ~3-times the time to complete than the present techniques and in a busy clinic, this translates into significant chair time for the patient. I fear that the accuracy benefit obtained using this technique may be over-ridden by the time taken to complete the task.

There may be a solution to this though. As indicated in the discussion section of the manuscript (lines 506 – 509), testing only one spatial frequency stimulus or a single disparity sign may reduce the time to complete the task. Given that the target spatial frequency did not have an impact on the stereoacuity anyways, can this not be implemented in the present version of the software and evidence provided that this indeed reduces the time to do the task? I understand that this involves additional data collection and more work for the authors, but this may be a significant step towards the holy-grail of having a test that is both accurate and can be administered quickly.

2. The stimuli used in the two new stereoacuity techniques is not clear to me. There are bandpass filtered ring and noise stimuli that the participants had to appreciate depth in. What was the pattern of depth though? I assume that in the ring stimuli, the “ring” appeared in depth depending on the stimulus disparity used but what was seen in the “noise” stimuli? This is not clear from the explanation. Perhaps a figure showing the two stimuli may be useful to include here for helping the readers understand the stimulus.

3. Other specific issues…

a. Abstract conclusion: Why only FlnD detected stereo deficits. It is also detected by AIM right? Please rephrase.

b. Abstract conclusion: The last statement is a rather superficial one. It should be replaced with a statement that describes the advantage/challenges of switching over to the new techniques proposed in this study, vis-a-vis, the existing ones. The new techniques take ~3times longer to complete than the routine clinical tests. What would be the motivation for the clinician to switch over to the new technique should come out clearly here.

c. Line 78: Add to this list that these tests are meant to be run at a constant viewing distance and are meant for a single IPD - the former limits their ability to check stereopsis at different viewing distances while the latter creates issues with test accuracy.

d. In general, the introduction is way too long (4.5 pages). This can be significantly shortened, without losing information.

e. Line 123: Expand HMD’s.

f. Lines 137 - 144: This section is a bit confusing. The start makes it appear as if there are only two experiments, but the remainder of the manuscript appears like there are five parts to the study. So, add a statement before first to indicate that what ensues is a note on the organization of the manuscript.

g. Line 170: I am sure this was taken care of, but a brief mention that there was no leak of information between the red/blue filters to reassure the readers. Also, how was the issue of blur arising from chromatic aberrations of the eye handled in these stimuli?

h. Line 195: Should this be log arc sec?

i. Lines 286 – 287: Please include a measure of variance of the data in all measures. Also, please fix the p=0.000 to p<0.001.

j. Line 292: Use of Box plots suggests that data were not normally distributed. Was that the case? If so, the results need to be presented as median and IQR.

k. Line 517: Be explicit that the new tests are faster, relative to the 2AFC paradigms.

l. Like the introduction section, the discussion section could also be tightened. In several areas of this section, the results are repeated, and this redundancy can be removed.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-27405R1Comparison of Foraging Interactive D-prime and Angular Indication Measurement Stereo with different methods to assess stereopsisPLOS ONE

Dear Dr. Neupane,

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.

==============================

ACADEMIC EDITOR:  Please address the minor comments raised by one of the reviewers.

==============================

Please submit your revised manuscript by May 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.

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,

Amithavikram R Hathibelagal, Ph.D.

Academic Editor

PLOS ONE

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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.

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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 #2: All comments have been addressed

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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 #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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 #2: Yes

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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 #2: Yes

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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: Really appreciate the effort taken to incorporate the changes into the manuscript.

The explanation of the aims is still not proper yet. What do the authors mean by two experiments? Was it the development of the FlnD and AIM? The author might want to avoid saying it's two experiments.

Figure 1 is impressive as it explains clearly, what the subjects would have been able to see. However, that makes me wonder why would the authors wanted to create these two stimuli. Authors might want to add a statement to indicate the pros of the ring and dip stimulus.

Lines 244 to 247 are a part of statistical analysis. Also in that section, it will be better to explain which variables were not normally distributed and that the authors have log-transformed the variable.

Usually, the F number is associated with two degrees of freedom not a single like F(5) and many more in the further text.

Fig 5 Are the correlation values Pearson’s correlations? Also, correlation is denoted with the symbol r. In the last review, when I suggested reporting the r2 values, I meant only for those instances where the correlation value was higher and the regression line could be fit and could have reported the r2 values then. In the same context, Line 39 in the abstract should say correlation instead of agreement.

Reviewer #2: The authors have addressed all the comments of the reviewers. The manuscript is much better organized now. I have nothing further to add to this review.

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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: No

Reviewer #2: Yes: Shrikant R Bharadwaj

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Comparison of Foraging Interactive D-prime and Angular Indication Measurement Stereo with different methods to assess stereopsis

PONE-D-23-27405R2

Dear Dr. Neupane,

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.

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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,

Amithavikram R Hathibelagal, Ph.D.

Academic Editor

PLOS ONE