Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Overall, the manuscript is informative, please find my comments below:
1. The title is OK.
2. For keywords, please revise that not all keywords are same with the title so bigger chance for reader to find your article
3. Add the novelty and gap of research in the abstract and introduction.
4. Is GSEBA ® the commercial products? If so, why would you not compare with your own formulation?
5. Add more clear explanation of statistical meaning * under the Table 1, 2, the present note is too simple. 
6. Please add literatures on line 309-316; and line 330-344
7. Add quantitative data in conclusion part, and also future work recommendations.

Author Response

Dear Reviewer,

Thank you very much for the time dedicated to evaluating our manuscript and for your positive feedback. We truly appreciate your constructive comments.

Regarding the keywords, they have now been revised and updated as suggested. We have also incorporated the novelty and research gap both in the abstract and in the introduction, ensuring clearer context and alignment with the scope of the study.

The legends of Table 1 and Tables 2 have been reformulated to improve clarity and adhere to your recommendations. In addition, several sections of the Discussion have been revised to provide stronger contextualization through additional references from the existing literature.

Finally, the Conclusion has been rewritten to include more quantitative considerations and to outline clearer recommendations for future research directions.

We thank you again for your valuable insights, which have significantly improved the quality of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

While the submitted manuscript reports clinical efficacies of anti-oxidant containing medical devices on inflammatory eczematous dermatitis, there are several points of major concern. 

• The inclusion criteria for participants, and disease information should be provided in more detail, i.e. location of lesions for each participants, how IGA was graded, what kinds of questionnaires were used for IDL.
• Detailed information for the test products should be described, including all the ingredients list and concentration of active ingredients (hyaluronic acid and GSH-C4).
• The authors stated that two different kinds of products were used for the study, but detailed information (how many participants used for each product) are also missing.
• Statistical analysis supporting the number of participants should be provided. 
• Theoretical rationale for the primary endpoint and secondary endpoint should be provided.
• RCM images shown in Figure 2 required through revision, including legends and image analysis details.
• While the authors stated that D-OCT image analysis showed a statistically significant change only at a depth of 150 μm, with no significant changes observed in other analyses, there are no corresponding images at 150 μm to support the authors’ interpretation. 

Author Response

Dear Reviewer,

Thank you very much for the time and attention dedicated to evaluating our manuscript. In response to your comments, we have substantially revised the entire Materials and Methods section, providing a more detailed description of the inclusion and exclusion criteria as well as a clearer explanation of the clinical and instrumental indices employed. We have also expanded the description of the statistical analysis and clarified the rationale for selecting the primary and secondary endpoints.

Figure 2 (RCM) is now accompanied by a fully detailed legend, and we have additionally included D-OCT images acquired at a depth of 150 µm, as requested.

We are grateful for your insightful remarks, which have significantly contributed to improving the quality and clarity of the manuscript.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

While the re-submitted manuscript is generally revised, there are still points of concerns not fully clarified. 

- Detailed information for the test products are still missing.

- Detailed information about the product usage (how many participants used for each product) are still missing. Do authors consider that two different formulations have same or similar activities? If so, are there any scientific evidences supporting this? 

- References supporting authors' description about deciding the primary endpoint and secondary endpoint should be provided.

- D-OCT analysis results are still not clear. Most of all, did authors analyzed all participants' data or just one participant? There are no data except "patient n12". Also, from the Figure 3 ~ 6, it looks that the vascular pattern has significantly improved for all of the measured depth. Without detailed information about the image analysis, authors' interpretation does not match the images shown in Figures. 

Author Response

Dear Reviewer,

We sincerely thank you for the careful evaluation of our manuscript and for the insightful comments provided. Your observations have been extremely helpful in improving the clarity, methodological robustness, and overall quality of the work. We have carefully addressed each point and revised the manuscript accordingly.

Comment: Detailed information for the test products are still missing.

Response: We thank the Reviewer for this remark. In the revised version, we have expanded the description of the test products in the “Test products” subsection of the Methods. We now specify that GSEBA® cream 1% and GSEBA® mousse 0.4% are non-steroidal topical medical devices formulated, respectively, as an oil-in-water cream and a foaming mousse. Both formulations contain humectants and soothing agents (such as glycerin and aloe vera juice), emollient esters and vegetable oils (e.g., coco-caprylate, olus oil, camelina sativa seed oil), rheology-modifying and conditioning polymers (ammonium acryloyldimethyltaurate/VP copolymer, polyquaternium-7), and a complex including hyaluronic acid, tocopheryl acetate (vitamin E) and N-butanoyl glutathione (GSH-C4), together with standard cosmetic excipients and propellants. A concise formulation description has been added to provide clearer information on the technological profile of the products without overloading the text with the full INCI list.

Comment: Detailed information about the product usage (how many participants used for each product) are still missing. Do authors consider that two different formulations have same or similar activities? If so, are there any scientific evidences supporting this?

Response: We thank the Reviewer for this helpful observation. We have now clarified in the Methods section how the two formulations were used and how many target areas received each product. In our cohort, GSEBA® cream 1% was systematically applied to face and body lesions, whereas GSEBA® mousse 0.4% was reserved for scalp involvement; overall, 25 of the 30 evaluated areas were treated with the cream and 5 with the mousse. Both formulations belong to the same medical device line, share the same active complex (GSH-C4 and hyaluronic acid), and are designed to target similar oxidative and inflammatory pathways. For this reason, the study was conceived as an exploratory, single-arm evaluation of the GSEBA® line rather than a head-to-head comparison between vehicles. We also acknowledge this aspect as a limitation in the revised Discussion, where we state that lesions treated with the two vehicles were analysed together, that the study was not powered or specifically designed to detect potential differences between cream and mousse, and that future larger head-to-head studies are warranted to formally compare the two formulations.

Comment: References supporting authors' description about deciding the primary endpoint and secondary endpoint should be provided.

Response: We thank the Reviewer for this helpful remark. In the revised manuscript, we have clarified that the choice of the primary and secondary endpoints was pre-specified and grounded in previously published studies. We have now added appropriate references in the Methods (Endpoints) section to support the use of the IGA as primary outcome, the selected time point of assessment, and the inclusion of pruritus and imaging parameters as secondary endpoints.

 

Comment: D-OCT analysis results are still not clear. Most of all, did authors analyzed all participants' data or just one participant? There are no data except "patient n12". Also, from the Figure 3 ~ 6, it looks that the vascular pattern has significantly improved for all of the measured depth. Without detailed information about the image analysis, authors' interpretation does not match the images shown in Figures.

Response: We thank the Reviewer for this comment. D-OCT was performed in all enrolled patients and on all 31 target areas at baseline and at the end of treatment; cohort-level quantitative D-OCT findigs are reported in the Results and summarized in Table X. The images in Figures 3–6 are representative examples and are not limited to patient n.12; for instance, Figure 3 refers to patient n.20, while patient n.12 is shown in another figure.

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Most of the comments were clearly addressed. However, reviewer still could not find the table X, showing the cohort-level quantitative D-OCT findings. 

Author Response

Thank you very much for your careful reading of our revised manuscript and for acknowledging the improvements already made. We apologize for the previous omission of the requested table. As suggested, we have now added Table 3, which reports the cohort-level quantitative D-OCT findings for all 31 target areas. This table summarizes the main vascular and stromal parameters at different depths and, in our opinion, provides substantial additional information that complements and strengthens the D-OCT results described in the text.