Transorbital Alternating Current Stimulation in Glaucoma: State of the Art from Neurophysiological Bases to Clinical Practice

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper introduces the residual activation theory and discusses the effects of electrical stimulation in glaucoma, highlighting the current limitations. It provides a valuable literature summary on trACS for the field. The manuscript is in good shape for publication after minor revisions.

Comment:

1. Please include reference numbers in Table 1 to enable readers to easily locate the corresponding papers.

2. Figure 3 is really helpful for understanding the residual activation theory. It would be beneficial to move Figure 3 closer to Section 2, where the residual activation theory is introduced.

3. The promising clinical results of trACS are exciting. However, there is a lack of consensus regarding its technical parameters (e.g., voltage, frequency) and treatment mechanisms. The discussion of the ex-vivo study by D.K. Freeman et al. has improved our understanding. Please include a discussion on whether any in vitro models (e.g., cell culture or tissue engineering models) have been or could be used for trACS research.

Helpful reference:

 

Lu R, Soden PA, Lee E. Tissue-Engineered Models for Glaucoma Research. Micromachines (Basel). 2020 Jun 24;11(6):612. doi: 10.3390/mi11060612. PMID: 32599818; PMCID: PMC7345325. 

Marcos LF, Wilson SL, Roach P. Tissue engineering of the retina: from organoids to microfluidic chips. J Tissue Eng. 2021 Dec 10;12:20417314211059876. doi: 10.1177/20417314211059876. PMID: 34917332; PMCID: PMC8669127.

Author Response

This paper introduces the residual activation theory and discusses the effects of electrical stimulation in glaucoma, highlighting the current limitations. It provides a valuable literature summary on trACS for the field. The manuscript is in good shape for publication after minor revisions.

Comment:

1. Please include reference numbers in Table 1 to enable readers to easily locate the corresponding papers.

Response:

We thank the reviewer for the suggestion aiming to improve the paper. We added the reference numbers in table 1.

2. Figure 3 is really helpful for understanding the residual activation theory. It would be beneficial to move Figure 3 closer to Section 2, where the residual activation theory is introduced.

Response:

We thank the reviewer for the comment and we modified the order of figures according to the suggestion.

3. The promising clinical results of trACS are exciting. However, there is a lack of consensus regarding its technical parameters (e.g., voltage, frequency) and treatment mechanisms. The discussion of the ex-vivo study by D.K. Freeman et al. has improved our understanding. Please include a discussion on whether any in vitro models (e.g., cell culture or tissue engineering models) have been or could be used for trACS research.

Helpful reference:

 

Lu R, Soden PA, Lee E. Tissue-Engineered Models for Glaucoma Research. Micromachines (Basel). 2020 Jun 24;11(6):612. doi: 10.3390/mi11060612. PMID: 32599818; PMCID: PMC7345325. 

Marcos LF, Wilson SL, Roach P. Tissue engineering of the retina: from organoids to microfluidic chips. J Tissue Eng. 2021 Dec 10;12:20417314211059876. doi: 10.1177/20417314211059876. PMID: 34917332; PMCID: PMC8669127.

Response:

We thanks the reviewer for the interesting comment. To the best of our knowledge there are no other paper improving the knowledge about the effect of trACS in vitro models. We added in the discussion some lines about recent development and insight of in vitro models, opening new possibilities to better understand trACS. May be this will represent a seed that will grow with the help of readers and researchers.

“In the last years a plethora of tissue have been engineered (e.g. skin, bone cornea, hearth) and a lot of efforts are ongoing to create more complex functional tissue as neural one, including retina. In this light, in order to create more complex structures, from simple 2D culture different labs created more complex 3D engineered tissues models and organoids resembling more closely the physiological structure and function of neural and retinal tissue. Moreover, new insight allowed the creation of the so-called microfluidic platform (or lab-on a chip), more simple of 3D models but with a highly 2D complexity than conventional 2D models. All these ex vivo models, also considering the further improvements, could be very helpful in order to increase the knowledge about the pathophysiological mechanism and the effect of trACS”.

 

Reviewer 2 Report

Comments and Suggestions for Authors

The paper „Transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice. A clinical review.“ Is within the scope of the Optics and it may be interesting for the readers. It has original idea, it is well-written and well-organized with interesting and visually attractive graphics. Some issues should be addressed before this paper is considered for publication.

1.       The title is simply to much with both „:“ and .“. Moreover the term clinical review means the following: “The clinical review is the most common type of evaluation in the health field. It is a review of the care received by a specific patient or family, performed because of interest in the welfare of this patient or family and to provide a basis for decisions on whether to continue, change, or stop treatment. The term clinical review is used here to refer only to this form of appraisal, which is a basic element of the clinical process. The care provided to individual patients may also be appraised (usually more formally) for other purposes, for example, as a technique for evaluating a health service.” This is literature review or state-of-the-art in this field or descriptive or narrative review. So, the titles that may be more appropriate are something like: “Review of the transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice.” Or “State-of-the-art in the transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice”

2.       If this is a narrative review and not systematic one, which according to the structure is, number 5 should not be discussion, but it should be addressed as something like 5. Clinical evidence of alternating current stimulation efficiency in low vision treatment, or something similar.

3.       The lines: 236-252 should be rewritten in accordance with the new title of the chapter. This practice is not in the guidelines but there are some reports about the efficiency of this kind of treatment given in the Table. Stick to that!

4.       Lines 264-336 should be rewritten. You should not paraphrase each paper but to somehow group the common nominator of the analyzed studies with the benefits of this type of treatment versus the limitations.

1.       The abstract and the conclusion should be improved after abovementioned lines are rewritten.

Author Response

The paper „Transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice. A clinical review.“ Is within the scope of the Optics and it may be interesting for the readers. It has original idea, it is well-written and well-organized with interesting and visually attractive graphics. Some issues should be addressed before this paper is considered for publication.

1. The title is simply to much with both „:“ and .“. Moreover the term clinical review meansthe following: “The clinical review is the most common type of evaluation in the health field. It is a review of the care received by a specific patient or family, performed because of interest in the welfare of this patient or family and to provide a basis for decisions on whether to continue, change, or stop treatment. The term clinical review is used here to refer only to this form of appraisal, which is a basic element of the clinical process. The care provided to individual patients may also be appraised (usually more formally) for other purposes, for example, as a technique for evaluating a health service.” This is literature review or state-of-the-art in this field or descriptive or narrative review. So, the titles that may be more appropriate are something like: “Review of the transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice.” Or “State-of-the-art in the transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice”

Response:

We thank the reviewer for his precise suggestion. According to the comment, we changed the title from “Transorbital alternating current stimulation in glaucoma: from neurophysiological bases to clinical practice. A clinical review” to “Transorbital alternating current stimulation in glaucoma: state of the art from neurophysiological bases to clinical practice”

2. If this is a narrative review and not systematic one, which according to the structure is, number 5 should not be discussion, but it should be addressed as something like 5. Clinical evidence of alternating current stimulation efficiency in low vision treatment, or something similar.
3. The lines: 236-252 should be rewritten in accordance with the new title of the chapter. This practice is not in the guidelines but there are some reports about the efficiency of this kind of treatment given in the Table. Stick to that!
4. Lines 264-336 should be rewritten. You should not paraphrase each paper but to somehow group the common nominator of the analyzed studies with the benefits of this type of treatment versus the limitations.
5. The abstract and the conclusion should be improved after abovementioned lines are rewritten.

Response:

We thank the reviewer for the time dedicated to the lecture of our review. In principle, we agree with the reviewer but we would like to underline that, while writing the paper, we had to consider the rules of the journal and according to that, a discussion was needed and mandatory. Please, consider also that we already sent to the journal a first version of the paper without discussion and we had to reshape the paper (with the new structure that you see now). For this reasons, we modified the title of paragraph 5 from “Discussion” to “Discussion, limitations and open issues” avoiding other more radical change of the paper structure (with the hope that for the editor this small change will be acceptable).

 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have made some changes and have ignored some recommendations without any comments. The most important comments were accepted and the paper has been modified in accordance with them.