Narrative Review Concerning the Clinical Spectrum of Ophthalmological Impairments in Parkinson’s Disease

Round 1

Reviewer 1 Report

Parkinson’s disease is a prevalent neurodegenerative disease for which there is no medication modifying the course of this disorder. In addition to motor symptoms Parkinson’s disease is associated with visual impairments the mechanism of which is not completely understood.  The authors describe various visual problems linked to Parkinson’s disease pathogenesis and propose putative mechanism of this association. This is an exciting area of biomedical research and the data discussed in the review will be interesting for the readers of “Neurology International”.

The following additions and corrections should be made.

 

Introduction

Lines 34-35: “The three primary symptoms of Parkinson’s disease are tremor at rest, stiffness, and

bradykinesia.” After this sentence the authors should add a citation of recent review on “Parkinson’s disease”: Emamzadeh  FN et al., Parkinson’s disease: Biomarkers, Treatment, and Risk Factors.”    Frontiers in Neuroscience, Neurodegeneration, 12, 61230, August 2018.     https://doi.org/10.3389/fnins.2018.00612

 

Lines 55-56: ”Alpha-Syn was reported to be aggregated in the inner nuclear, inner plexiform, and ganglion cell layers of the intraretinal area in a research [6].” The style of the sentence should be corrected as follows: ”Ortuño-Lizarán demonstrated that Alpha-Syn was aggregated in the inner nuclear, inner plexiform, and ganglion cell layers of the intraretinal area [6].

 

Materials and Methods

Line 77-78:  Among 1970 and 2022, English publications containing the terms "optic," "ophthalmology," and "ocular" in relation to "Parkinson's disease" and "PD" were recognized as being relevant. This awkward sentence should be rewritten as follows: ”Publications in English between 1970 and 2022 containing the terms "optic," "ophthalmology," and "ocular" in relation to "Parkinson's disease" and "PD" were included in our selection.”

 

3. Pathogenesis of Parkinson’s disease

Lines 96-97: ”Recent breakthroughs in PD genetics have highlighted the importance of mitochondrial dysfunction in PD development”. The authors should add reference(s) after this sentence.

 

Lines 108-110: ”The substantia nigra might be more susceptible to such situations, and extensive research reveals fascinating variations in the expression of genes participating in energy consumption between dopamine neurons of the substantia nigra and other dopamine neurons [15]”. The sentence is awkward; it can be rewritten as follows: ” The substantia nigra is more susceptible to such deficiency, and extensive research reveals multiple variations in the expression of genes controlling energy consumption between dopamine neurons of the substantia nigra and elsewhere” [15].

3.3 Lines 124-125: ”Multiple hypotheses postulate that oxidative stress contributes to the pathogenesis

of Parkinson's disease, and that greater susceptibility to oxidative stress could make particular cell types more susceptible to damage in PD.” Reference(s) should be added after the sentence.

 

There is discrepancy between the text on Lines 160-162” and references 28, 29:

 

Lines 160-162:” Nevertheless, other researchers have not replicated similar findings, and Ahlskog and colleagues observed no significant rise in malondialdehyde levels in the plasma of Parkinson's disease

patients in comparison to controls [28, 29].”

Ahlskog et al are not in references 28- 29. Furthermore malondialdehyde levels are not in references 28-29.

 

28. Reiszadeh Jahromi, S.; Ramesh, S.R.; Finkelstein, D.I.; Haddadi, M. Α-Synuclein E46K Mutation and Involvement of Oxidative Stress in a Drosophila Model of Parkinson’s Disease. Parkinsons Dis. 2021, 2021, 6621507, doi:10.1155/2021/6621507.

Neurol. Int. 2023, 15, FOR PEER REVIEW 18

29. Nakabeppu, Y.; Tsuchimoto, D.; Yamaguchi, H.; Sakumi, K. Oxidative Damage in Nucleic Acids and Parkinson’s Disease. J. Neurosci. Res. 2007, 85, 919–934, doi:10.1002/jnr.21191.

 

Conclusion

Line 683. “Certain visual disorders may represent initial symptoms of Parkinson's disease or even early clinical indicators.” This is an important statement. The authors should add their ideas what visual biomarkers can be used for diagnosis or early detection of Parkinson’s disease. Data from references 6, 7 and others may be discussed.

Author Response

Dear Reviewer,

 

Thank you very much for your help and guidance. We tried to follow all your suggestions. We are hoping that the modifications we made are fulfilling your expectations.

 

Thank you!

 

 

Reviewer 1

 

Parkinson’s disease is a prevalent neurodegenerative disease for which there is no medication modifying the course of this disorder. In addition to motor symptoms Parkinson’s disease is associated with visual impairments the mechanism of which is not completely understood.  The authors describe various visual problems linked to Parkinson’s disease pathogenesis and propose putative mechanism of this association. This is an exciting area of biomedical research and the data discussed in the review will be interesting for the readers of “Neurology International”.

The following additions and corrections should be made.

 

Introduction

Lines 34-35: “The three primary symptoms of Parkinson’s disease are tremor at rest, stiffness, and bradykinesia.” After this sentence the authors should add a citation of recent review on “Parkinson’s disease”: Emamzadeh  FN et al., Parkinson’s disease: Biomarkers, Treatment, and Risk Factors.”    Frontiers in Neuroscience, Neurodegeneration, 12, 61230, August 2018.     https://doi.org/10.3389/fnins.2018.00612

 

Done, thank you! (line 36)

 

Lines 55-56: ”Alpha-Syn was reported to be aggregated in the inner nuclear, inner plexiform, and ganglion cell layers of the intraretinal area in a research [6].” The style of the sentence should be corrected as follows: ”Ortuño-Lizarán demonstrated that Alpha-Syn was aggregated in the inner nuclear, inner plexiform, and ganglion cell layers of the intraretinal area [6].

 

 Done, thank you! (line 58)

 

Materials and Methods

Line 77-78:  Among 1970 and 2022, English publications containing the terms "optic," "ophthalmology," and "ocular" in relation to "Parkinson's disease" and "PD" were recognized as being relevant. This awkward sentence should be rewritten as follows: ”Publications in English between 1970 and 2022 containing the terms "optic," "ophthalmology," and "ocular" in relation to "Parkinson's disease" and "PD" were included in our selection.”

 

Done, thank you! (line 82)

 

3. Pathogenesis of Parkinson’s disease

Lines 96-97: ”Recent breakthroughs in PD genetics have highlighted the importance of mitochondrial dysfunction in PD development”. The authors should add reference(s) after this sentence.

  

Done, thank you! (line 117)

 

 

Lines 108-110: ”The substantia nigra might be more susceptible to such situations, and extensive research reveals fascinating variations in the expression of genes participating in energy consumption between dopamine neurons of the substantia nigra and other dopamine neurons [15]”. The sentence is awkward; it can be rewritten as follows: ” The substantia nigra is more susceptible to such deficiency, and extensive research reveals multiple variations in the expression of genes controlling energy consumption between dopamine neurons of the substantia nigra and elsewhere” [15].

 

Done, thank you! (line 130)

 

3.3 Lines 124-125: ”Multiple hypotheses postulate that oxidative stress contributes to the pathogenesis

of Parkinson's disease, and that greater susceptibility to oxidative stress could make particular cell types more susceptible to damage in PD.” Reference(s) should be added after the sentence.

 

Done, we omitted to cite the references. (line 149)

 

There is discrepancy between the text on Lines 160-162” and references 28, 29:

Lines 160-162:” Nevertheless, other researchers have not replicated similar findings, and Ahlskog and colleagues observed no significant rise in malondialdehyde levels in the plasma of Parkinson's disease

patients in comparison to controls [28, 29].”

Ahlskog et al are not in references 28- 29. Furthermore malondialdehyde levels are not in references 28-29.

28. Reiszadeh Jahromi, S.; Ramesh, S.R.; Finkelstein, D.I.; Haddadi, M. Α-Synuclein E46K Mutation and Involvement of Oxidative Stress in a Drosophila Model of Parkinson’s Disease. Parkinsons Dis. 2021, 2021, 6621507, doi:10.1155/2021/6621507.

Neurol. Int. 2023, 15, FOR PEER REVIEW 18

29. Nakabeppu, Y.; Tsuchimoto, D.; Yamaguchi, H.; Sakumi, K. Oxidative Damage in Nucleic Acids and Parkinson’s Disease. J. Neurosci. Res. 2007, 85, 919–934, doi:10.1002/jnr.21191.

 

An error was made, therefore, we have removed the sentence ” Nevertheless, other researchers have not replicated similar findings, and Ahlskog and colleagues observed no significant rise in malondialdehyde levels in the plasma of Parkinson's disease patients in comparison to controls [28, 29].”

 

Conclusion

Line 683. “Certain visual disorders may represent initial symptoms of Parkinson's disease or even early clinical indicators.” This is an important statement. The authors should add their ideas what visual biomarkers can be used for diagnosis or early detection of Parkinson’s disease. Data from references 6, 7 and others may be discussed.

 

Thank you for the suggestion, we have added more information in the „Conclusions„ section-

 

„For instance, multiple studies indicate a link between modifications in the retina and pathological brain alterations in Parkinson's disease, suggesting the retina as a possible biomarker for the diagnosis of PD considering the reduction of dopamine neurons in the retinal cells of Parkinson's disease patients. Neuropathological, morphological, and electrical abnormalities in the PD retina, as well as phosphorylated Alpha-Syn aggregation in the PD retina, provide evidence that the retina may serve as a biomarker for Parkinson's disease. The evaluation of the retina in PD patients can be easily performed through optical coherence tomography, which is an investigation that usually discovers the abnormalities of the retina that are linked to the PD. Nevertheless, more imaging investigations are required to validate these observations.”

Author Response File: Author Response.docx

Reviewer 2 Report

Stuparu et al. realized a very interesting review describing the “Narrative review concerning the clinical spectrum of ophthalmological impairments in Parkinson’s disease”. I consider the manuscript very interesting but, at the same time, I suggest several revisions needed to improve the reliability and the completeness of the paper: 

·      The “Introduction” sections should be more updated and improved. I suggest adding data related to the involvement of oxidative stress and their possibly related components, especially vascular ones. The recent PMID: 32877751, PMID: 30523548, PMID: 36490268 and PMID: 36290689 could represent a substrate able to enforce the role of considered cellular mechanisms.

·      Finally, manuscript requires important English revisions and typos correction. 

Author Response

Dear Reviewer,

 

Thank you very much for your help and guidance. We tried to follow all your suggestions. We are hoping that the modifications we made are fulfilling your expectations.

 

Thank you!

 

 

 

Stuparu et al. realized a very interesting review describing the “Narrative review concerning the clinical spectrum of ophthalmological impairments in Parkinson’s disease”. I consider the manuscript very interesting but, at the same time, I suggest several revisions needed to improve the reliability and the completeness of the paper:

• The “Introduction” sections should be more updated and improved. I suggest adding data related to the involvement of oxidative stress and their possibly related components, especially vascular ones. The recent PMID: 32877751, PMID: 30523548, PMID: 36490268 and PMID: 36290689 could represent a substrate able to enforce the role of considered cellular mechanisms.

 

            Thank you for your suggestions. We have added information from the articles that match our subject, and we have cited all the articles recommended by you in the references [18-21]. 

 

 

 

 

• Finally, manuscript requires important English revisions and typos correction.

 

The manuscript was corrected and verified by an English native speaker.

Author Response File: Author Response.docx