PONE-D-24-24404

Changes in the distribution of the tear lipid layer after intensive pulse light combined meibomian gland expression in patients with meibomian gland dysfunction

PLOS ONE

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Additional Editor Comments:

The manuscript has been evaluated by three reviewers, and their comments are available below.

The reviewers have raised a number of concerns that need attention. They request additional information on methodological aspects of the study, revisions to the statistical analyses and improved discussion.

Could you please revise the manuscript to carefully address the concerns raised?

Comments from PLOS Editorial Office: We note that one or more reviewers has recommended that you cite specific previously published works. As always, we recommend that you please review and evaluate the requested works to determine whether they are relevant and should be cited. It is not a requirement to cite these works. We appreciate your attention to this request.

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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: No

Reviewer #2: Yes

Reviewer #3: No

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: I Don't Know

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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: Yes

Reviewer #3: 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

Reviewer #3: No

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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: The purpose of this retrospective study was to examine changes in DED characteristics and lipid-layer distribution after IPL and MGX treatment in MGD patients. They examined 218 MGD patients who received IPL and MGX therapy. A Placido-disc-based tear film analyzer and slit lamp were used to assess differences in DED characteristics, LLT, avg LLT differences in inferior corneal pictures were evaluated by splitting them into upper, lower, nasal, and temporal quadrants, then into six sections from top to bottom using Python. After 3 IPL therapy OSDI, MG expressibility, and quality scores improved. DED symptoms improved, except for fluorescein-stained tear meniscus height. Redness in the nasal limbal and bulbar conjunctiva decreased markedly, but not in the total conjunctiva. IPL therapy increased mean LLT. The LLT grew dramatically in the upper half of the photos, but not in the lower half. The difference in LLT between halves reduced significantly. Post-IPL treatment, lipid-layer distribution discrepancies diminished in the uppermost region after picture segmentation. The study concludes that IPL and MGX treatment improved lower tear lipid-layer stasis and vertical lipid distribution in MGD patients. The Placido tear film analyzer can be used for assessing lipid-layer distribution in MGD.

I would like to compliment the authors on their interesting manuscript. However, several points and comments have to taken into consideration prior to publication.

1. Lines 31-32: “Slit-lamp-measured DED signs also increased, except for the fluorescein-stained tear meniscus height.” Please clarify, rather than increase/decrease, please write improved/worsened for clarity.

2. Lines 24: The study lacks a control group for definitive clinical conclusions. Please justify the lack of a control group and conclusions of the study.

3. Lines 106: Please clarify this “Lipid-layer image analysis”, aspect of the study. It’s not clear whether the authors are assessing the colors changes or deriving the thickness of TFLL from the interferometric patters obtained by the Keratograph 5M. While its clear that color changes equate to LLT please explain for readers how the changes equate to thickenss.

4. Furthermore, is the Total LLT= LLT inferotemporal+LLT superotemporal + LLT inferonasal + LLT superonasal or the mean of all these regions?

5. Please justify the use of lower half of the cornea for image analysis and its clincal significance.

6. It would be more substantial if the authors could compare their LLT with devices such as Lipiview, etc. If not possible please discuss.

7. Table 2 shows the changes in various clinical characteristics of dry eye, it hasn’t been mentioned how these changes effects the LLT regions or Horizontal difference of LLT. Possible this might bring out the clinical significance of this study, any correlation or risk factors. Please include it in the discussion:

a. Song, Yilin, et al. "Tear film interferometry assessment after intense pulsed light in dry eye disease: A randomized, single masked, sham-controlled study." Contact Lens and Anterior Eye 45.4 (2022): 101499.

b. Ahmed, S. et al. (2019). Effect of intense pulsed light therapy on tear proteins and lipids in meibomian gland dysfunction. Journal of ophthalmic & vision research, 14(1), 3.

c. Zhao, Hui, et al. "Lipidomics profiles revealed alterations in patients with meibomian gland dysfunction after exposure to intense pulsed light." Frontiers in Neurology 13 (2022): 827544.

8. Figure 1 should a detailed “study design and process” figure.

9. While figure 1 and figure 2 are interesting, these are averaging the pixels, please state clearly how many pixels were used to make each quadrant. How did the authors eliminate biases while performing this analysis as not all eyes are of the same size and the focal length of the patient is not regular. Furthermore, the iris of patients are of various color intensities.

10. Figure 2 contains 3 panels, please simplify by labeling them as A, B, C. Same with figure 1 that has 2 panels.

11. Figure 2 C is a line graph that has to has to have more description. i.e the x-axis and y-axis are not apparently clear to the reader.

12. Lines: 204. The hypothesis has not taken into consideration that the upper half of the cornea was not assessed and what are the pro and cons of this approach.

13. As stated in lines 224 this is a novel study, however, the lipid layer is a structure floating on the aqueous and mucin layers, the author has to assess the interplay of the various layers and whether the other layers (TMH volume, TBUT integrity, MG expressibility, MGquality had any influence on their findings.

Reviewer #2: I sincerely appreciate the opportunity to read and evaluate the authors research on tear lipid layer with IPL and meibomian gland expression. I’ve been privileged to review several dozen dry eye papers to date in addition to publishing several on the topic; in light of this, and although there may be hetereogeneity in measurements, patients, and follow up, this paper ranks among the top 1% on the topic in terms of scientific rigor and methodology. Very impressive, and a congratulations to the authors are in order.

Please see below for my comments:

Abstract: Line 50 should read“is a widely used treatment…” remove the word “most”

Intro does a great job at laying out the landscape of dry eye and adequately addresses the niche and need for this paper.

Methodology includes IRB and ethics review.

Dry eye protocols are quite rigorous and standardized, very impressive.

Language is concise.

Results: While it does say who did the IPL, does it say who did the exams?

The sole critique and question that I have is maybe the authors should include the NNT statistic based on the primary outcome. Also for those statistically significant differences on secondary outcomes was Bonferroni performed? If not, you may see that statistical significance disappeares due to the small difference between the groups, and the fact that it helps to adjust p-values and mitigate the risk of Type I errors arising from conducting numerous statistical tests on the same dataset.

Otherwise a brilliant study and look forward to the response.

Reviewer #3: Friday, January 3

Dear Editor

Thank you for the invitation to review the manuscript titled: Changes in the distribution of the tear lipid layer after intensive pulse light combined meibomian gland expression in patients with meibomian gland dysfunction.

The aim of the study is to investigate changes in dry eye disease (DED) parameters and lipid-layer distribution after treatment with intensive pulse light combined with Meibomian gland expression treatment in patients with Meibomian gland dysfunction (MGD). After reviewing the manuscript, I think it requires a major revision to be suitable for publication in your admired journal. However, some comments to the author are presented below to improve the manuscript:

Materials and Methods

1. Page 5, lines 39-35: please clear the treatment periods (What is the interval between sessions, and why were the measurements done two weeks after IPL, not earlier?

2. The method should explain the light parameters used during IPL therapy using an acne filter, such as the emitted light wavelength, light intensity, operating voltage, power, frequency, maximum optical energy, pulse duration, and repetition time or any data regarding the instrument used.

3. The author mentioned in the abstract that: This retrospective study included 218 patients diagnosed with MGD, while in the result section (Page 7, line 128), he mentioned the number of patients was 337. In addition, the number of patients should be added obviously in the method section.

4. In the discussion section, pages 10-11, from lines 182-194, there are obvious overlaps. These paragraphs can be summarized in one or two sentences only.

5. Page 13, lines 232-236: there was no relation between the two sentences about the treated eyes and the healthy individuals. Please try to find another reference to support your data.

6. Page 13, lines 241-242. The distribution of the lipids layer is affected by blinking as each time the eye blinks, the lipid layer on the surface of the eye is compressed and then steadily expands, which creates a non-equilibrium state, and affects the reorganization of the lipid layers. The author should enrich the discussion with previous studies regarding tear lipids as PMID: 30820280 and other previous studies.

7. The results obtained are not discussed carefully in the discussion section in addition to the weaknesses in the correlation between the obtained results and the previous literature.

Best Regards

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Changes in the distribution of the tear film lipid layer after intensive pulsed light combined with meibomian gland expression in patients with meibomian gland dysfunction

PONE-D-24-24404R1

Dear Dr. Choi,

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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Kind regards,

Kofi Asiedu, O.D., Ph.D.

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 #2: All comments have been addressed

Reviewer #3: 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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: I Don't Know

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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

Reviewer #3: 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

Reviewer #3: 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: I have no comments; the authors seems to have addressed all previous concerns to the best of their ability.

Reviewer #2: Authors have meticulously addressed all my concerns, and by the looks of it, the other editors' concerns as well.

Reviewer #3: Monday, January 27

Dear Editor

It is an honor to have been invited by you to re-review the manuscript “Changes in the distribution of the tear lipid layer after intensive pulse light combined meibomian gland expression in patients with meibomian gland dysfunction.”

I appreciate the opportunity to contribute to improving this manuscript as the author followed the comments point by point. After these revisions, the manuscript is suitable to be accepted in your admired journal “Plos One.”

Best regards

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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

Reviewer #3: No

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