Toxic External Exposure Leading to Ocular Surface Injury

Round 1

Reviewer 1 Report

Dear Editor,

The following are my comments on manuscript ID vision-2267384.

In this review, Steven H. Rauchman et al. provides a comprehensive and logical update and summary of the current literature regarding the various types of external threat that result in ocular surface injury. From a broad perspective, eye surface injury is a key branch of ocular trauma including three major topics, toxic threat, the mechanism of injury and wound healing, and acute and long-term management and treatment. This review focuses on the types of external toxic substances, such as pollution effects, airbag deployment, pesticide exposure, and workplace ocular injuries. It is visionary that authors consider climate change as a major threat and this review reflects the related latest research in the field.

If there is room for improvement and better reader experience, I would suggest authors modify the schematic figure to list all the major and relevant external threats on the left side and put the diagram of the anterior segment of the eye on the right side. It will be a clear and concise way to present this review.

In addition, I believe the topic is limited to the ocular surface tissues. Therefore, the evidence from retinal pigment epithelium cells (reference 263) may not be relevant here. 

Author Response

We thank the reviewer for thoroughly scrutinizing our manuscript. As requested, we have revised the manuscript and addressed the specific comments of the reviewer. The revised sections are delineated in red in a marked copy of the manuscript text.

Below, we provide a point-by-point response to the reviewer’s comments.

Reviewer 1:

Comment 1: In this review, Steven H. Rauchman et al. provides a comprehensive and logical update and summary of the current literature regarding the various types of external threat that result in ocular surface injury. From a broad perspective, eye surface injury is a key branch of ocular trauma including three major topics, toxic threat, the mechanism of injury and wound healing, and acute and long-term management and treatment. This review focuses on the types of external toxic substances, such as pollution effects, airbag deployment, pesticide exposure, and workplace ocular injuries. It is visionary that authors consider climate change as a major threat and this review reflects the related latest research in the field.

Response: We thank the reviewer for these kind words.

Comment 2: If there is room for improvement and better reader experience, I would suggest authors modify the schematic figure to list all the major and relevant external threats on the left side and put the diagram of the anterior segment of the eye on the right side. It will be a clear and concise way to present this review.

Response: We appreciate this suggestion and have revamped Figure 1 accordingly.

Comment 3: In addition, I believe the topic is limited to the ocular surface tissues. Therefore, the evidence from retinal pigment epithelium cells (reference 263) may not be relevant here.

Response: We agree and have removed the reference and added a new reference (Fukuoka et al.) and brief discussion of UV blocking contact lenses as protection for lens and cornea.

Author Response File: Author Response.pdf

Reviewer 2 Report

In this review the  authors highlighted the role of several envoenmental  toxic agents  in triggering  eye damage.

After an update on the test for evaluation of ocular toxicity, starting by Draize test , banned by actual regulations, coming to in vitro validated test such reconstructed human cornel epithelium, and the actual relevance of in silico models for a rapid prediction of relationships on structure/activity, without animal testing.

The environmental toxins can act at level of several ocular targets, such as cornea, limbus, conjunctiva, and tear film. Among these stressors the authors gave a high relevance to air pollutants. In particular   ozone which induced severe ocular inflammatory disease via oxidative stress. Also the matter of particulate is relevant in this issue: fine particulate is responsible of dry eye syndrome by increase of proinflammatory cytokines/chemokines as well  oxidative stress which palya relevant role in cellular damage and consequently death. Similar ways of toxic action is played by nitrogen oxides. Moreover also mixtures of combustion-derived pollutants  can damage ocular surface in similar manner.

Pesticides, herbicides and insecticides interfere with several biological pathways which can lead to oxidative stress, while fungicides, containing different metal or organphosphates,  can interfere with ATP synthesis, neural AChE.  

The authors referred also the damages derived from air bag deployment which  can release dangerous fragments that can also cause mechanical damage as well  foreign materials derived from work activities or environmental accidents. It is to underlien that metallic objects can relase iron, copper and othe metal ions which are consider a relevant players  in inducing glaucoma, cataracts and retina alterations.

It is well known the role of alkalis and acids  in damaging eyes by direct contact, and the authors reported a summary table on the relevant charateristics of chemical burns, indicating the chemical compound and the sources.

The authors showed also an  interesting issue about the key features of climate changes, including elevated global temperature , UV, CO2, ozone depletion , the quality of air in general referring to pollutants, smoke, atmosheric dust and  allergens in the air. All these factors are related to an increase of  inflammatory process on humanhealth including eye homeostasis.

taken together these issues the authors underlined how it is critical to identify these stressor  exposures and the associated risks  for human health as well to protect our vision  

Author Response

We thank the reviewer for thoroughly scrutinizing our manuscript.

Below, we provide a point-by-point response to the reviewer’s comments.

Reviewer 2:

Comment 1: Taken together these issues the authors underlined how it is critical to identify these stressor exposures and the associated risks  for human health as well to protect our vision 

Response: We are so gratified that the reviewer found our article informative and appreciate the beautifully written summary of our article.

Author Response File: Author Response.pdf