Ocular Motility Abnormalities in Ehlers-Danlos Syndrome: An Observational Study

Round 1

Reviewer 1 Report

The article is very interesting for people dealing with Ehlers-Danlos syndrome (EDS). It also enlarges our general knowledge about this syndrome. Oculomotoric disturbances haven't been reported on such a large group of EDS patients until now. 

I have not any essential and formal remarks.

Some small language errors should be corrected during the editing process.

Author Response

 Thank you very much for reviewing our manuscript and for your positive comment. Small language errors in the text were corrected.  

Reviewer 2 Report

The article “Ocular motility abnormalities in Ehlers-Danlos Syndrome:  observational study” presents the findings of a cross-sectional study that aimed to evaluate ocular motility (OM) abnormalities associated with Ehlers-Danlos Syndrome (EDS). The study included 81 patients who underwent a complete orthoptic examination, which involved a range of tests to assess OM, such as the corneal light reflex test, stereoscopic test, cover test, evaluation of eye pain in different gaze positions, and red filter test for diplopia. The study found that patients with EDS showed various OM alterations, specifically superior and medial rectus muscles hypofunction. The article concludes that a full orthoptic evaluation in these patients is recommendable to detect OM involvement and possible ligamentous laxity changes over time through an accurate OM assessment.

 

The article provides a comprehensive overview of EDS, including its clinical and genetic features, and outlines the various ocular manifestations of the condition. The results are presented in a clear and concise manner, highlighting the prevalence of OM abnormalities in patients with EDS, including the specific muscles that are affected.

However, the article could benefit from a more detailed discussion of the clinical implications of the findings. 

Other remarks:

Please revise the title. An all-caps title is not aesthetically pleasing.

Please use the proper reference formatting.

I noticed that there are several separate paragraphs that should be combined, as they are related to the same topic.

Materials and Methods

I recommend moving the age of the study population along with its standard deviation to the Materials and Methods section.

 

Table 1 & Table 2

What is the meaning of the value 0? Please consider using an acronym where no hyperfunction is diagnosed since now it is not clear whether the information is missing or there are no hyperfunctions.

 

"In our sample these alterations in OM, cannot be correlated to a compromised binocular vision, because motor fusion was within the normal limits and stereopsis, although in some cases coarse, was present."

 

I agree, the Lang test can in many cases is not precise (it can estimate down to 200" arcsec, which is not enough for fine stereopsis) and subjective especially in children or cognitively impaired patients.  I will recommend that the authors discuss the possibility to measure fine stereoacuity by measuring reflexive Ocular Following Responses (OFRs) (see 10.1167/18.4.7 and 10.1371/journal.pone.0277443). These studies have shown promising results, indicating that OFRs may provide more precise information on an individual's binocular vision, stereopsis and binocular summation, which can be obtained from eye movement. I think it would be valuable for the authors to discuss the potential for using OFRs as a future development in binocular vision assessment, especially in the population where verbal feedback is hard to obtain, which might resolve the issue in the sentence above. 

 

Additionally, the article could discuss the limitations of the study, such as the small sample size, which could impact the generalizability of the findings.

Overall, the article provides important insights into the ocular manifestations of EDS and highlights the importance of a comprehensive evaluation in patients with this condition.

Author Response

Thank you very much for reviewing our manuscript and for your  comments. Here you can find a point-by-point response to the comments.

-The article provides a comprehensive overview of EDS, including its clinical and genetic features, and outlines the various ocular manifestations of the condition. The results are presented in a clear and concise manner, highlighting the prevalence of OM abnormalities in patients with EDS, including the specific muscles that are affected. However, the article could benefit from a more detailed discussion of the clinical implications of the findings.

A: We have extended the discussion as suggested, showing the clinical implications of our findings.

-Please revise the title. An all-caps title is not aesthetically pleasing.

A: Amended. We have revised the title as suggested.

-Please use the proper reference formatting.

A: Amended. We have used the proper reference formatting.

-I noticed that there are several separate paragraphs that should be combined, as they are related to the same topic.

A: Amended. The paragraphs related to the same topic were combined.

-Materials and Methods. I recommend moving the age of the study population along with its standard deviation to the Materials and Methods section.

A: We have moved it as suggested.

-Table 1 & Table 2. What is the meaning of the value 0? Please consider using an acronym where no hyperfunction is diagnosed since now it is not clear whether the information is missing or there are no hyperfunctions.

A: The meaning of value 0 is that no hyperfunction/hypofunction was observed, that is N=0 as we have indicated in Table 1 and 2 

-"In our sample these alterations in OM, cannot be correlated to a compromised binocular vision, because motor fusion was within the normal limits and stereopsis, although in some cases coarse, was present."I agree, the Lang test can in many cases is not precise (it can estimate down to 200" arcsec, which is not enough for fine stereopsis) and subjective especially in children or cognitively impaired patients.  I will recommend that the authors discuss the possibility to measure fine stereoacuity by measuring reflexive Ocular Following Responses (OFRs) (see 10.1167/18.4.7 and 10.1371/journal.pone.0277443). These studies have shown promising results, indicating that OFRs may provide more precise information on an individual's binocular vision, stereopsis and binocular summation, which can be obtained from eye movement. I think it would be valuable for the authors to discuss the potential for using OFRs as a future development in binocular vision assessment, especially in the population where verbal feedback is hard to obtain, which might resolve the issue in the sentence above. 

A: We have added in the discussion, as suggested, the possible role of OFR in the evaluation of binocular vision and inter-eye collaboration, through the analysis of eye movements.

-Additionally, the article could discuss the limitations of the study, such as the small sample size, which could impact the generalizability of the findings.

A: As you suggested, the limitations of the study have been added in discussion. 

Reviewer 3 Report

This is a very interesting article 

Author Response

Thank you very much for reviewing our manuscript and for your positive comment. 

Reviewer 4 Report

 An ophthalmological and orthoptic evaluation should be performed in all patients with Ehlers-Danlos syndrome to detect and treat ocular motility disorders. 

The big data collected by the authors in the present  manuscript confirm  the previous sentence that can be reached in several textbook of ophthalmology. 

Author Response

 Thank you very much for reviewing our manuscript and for your positive comments. 

Round 2

Reviewer 2 Report

Dear Authors,

Thank you for your responses.

I believe that your responses have adequately addressed all of the issues raised in your publication and have strengthened the overall quality and impact of your research.