Low-Concentration Atropine Monotherapy vs. Combined with MiSight 1 Day Contact Lenses for Myopia Management

Round 1

Reviewer 1 Report

Line 23 – MiSight lenses are referred to “Dual-focus” by the manufacturer rather than double focus.

Line 65 – the more precise term is “efficacy” not efficiency

Lines 70-72 – the mechanism by which atropine slows myopia is not known. Even with the citation, it does not support the ability to say how atropine slows myopic progression.

Both Table 1 and Table 2 require statistical analysis that includes p-values to establish statistical vs clinical significance.

Line 190 – reporting of axial elongation is reported here using a minus sign. There needs to be consistency throughout the paper. If in fact it is (-) that would indicate a shortening of axial length. Please correct and make consistent in all reporting of axial length changes.

In the methods, there was no mention of how the subjects were assigned to each group. It needs to be described as it is a source of potential bias.

As the authors mentioned regarding study limitations, there are a number of factors that make it difficult to draw conclusions from these data. 1) Age – the range in age is so large that the difference in progression between an 8 and 15 yr old may sway the results. There should be tighter age range to be able to draw any conclusions. 2) Small numbers – with 20 -30 in each group, it also creates a condition that make conclusions not credible. 3) Ethnicity – there was no mention of subjects ethnic background and previous studies show significant differences in rate of progression in different populations. The conclusions need to be re-worded to prevent readers from taking the data as a strong basis for treatment decisions of individual patients.

Finally, in statistical analysis it would be extremely helpful to see the cumulative effects of treatment in the treatment groups vs. the controls over the study period.

Author Response

Responses in file. Thank you for the opportunity to improve our work

Author Response File: Author Response.pdf

Reviewer 2 Report

This is a very interesting paper, very well written and with adequate referencing. As myopia treatments develop in variety and many options may appear, knowledge of the possible benefit of combination therapies is of urgent need so this paper is welcome. As increasing outdoor exposure can decrease incidence and arrest progression it would be nice if authors gather information of outdoor exposure of their subjects in the future and perform an analysis of whether patterns of outdoor exposure affect treatment options. Only minor comments about the text. And congratulations for such a nice paper.

LINE 49. It was thought that myopia con stop progression at age 16 but a recent consensus has established age 25 as the most probable age for stable myopia. https://revistaoce.com/index.php/revista/article/view/160/247

The use of Tropicamide instead of cycloplentolate should be discussed as it is generally believed that the last one produces better cycloplegia.

Part 3.1 onwards should be Discussion….

LINE 190. Was that difference significant although of not clinical relevance?

Author Response

Responses in file. Thank you for the opportunity to improve our work

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Line 48 – needs re-wording…. The word development rate is confusing. Does that mean incidence or rate of progression. If it refers to rate of progression, the statement is incorrect as rate of progression is fastest at younger ages and at the time myopia is first seen (age7-11 ?).

Line 77 – If 0.05% is the preferred concentration in the cited papers, why was the study done with 0.01% ?

The table lists the mean SE of 4.81 with a range for the Atropine group as 1.25 to 10.875 and the Atropine + DFCL as mean SE of 4.14 with a range of 1.625 to 6.00 but in the text, means are both listed as 4.81 and the range for the combination group is stated at 1.25 to 10.875.

Please correct one of them.

Line 186 – minor point but, the word mydriasis should be changed to cycloplegia as that intent of the drops.

In the discussion, under method considerations, the points raised are really strengths or weaknesses of the study. Rather than “considerations” they should be described in the headings as strengths/weaknesses.

Although the discussion of OrthoK is somewhat related to the current study, it seems out of place and not applicable to the purpose of this paper. Consider removing this.

Discussion need to address three more points: 1) Most studies on myopia progression use objective cycloplegic refraction as an outcome measure rather than subjective cycloplegic refraction. Please discuss the reasons and potential issues this raises. 2) As stated in the introduction, 0.05% is recommended as the ideal dosage for slowing axial elongation from a number of studies. Discuss why 0.01% was chosen for this study.3) The gold standard for myopia progression studies is axial length. Please discuss the issues that come into play when using refractive results as an outcome measure.

Author Response

Thank you for the opportunity to improve our manuscript. The point by point responses are attached here and the changes have been highlighted in the manuscript. The sources have also been updated.

Author Response File: Author Response.docx