Beauty’s Blind Spot: Unmasking the Ocular Side Effects and Concerns of Eye Cosmetics

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Congratulations to the authors for the manuscript. It would be good to support the content of the manuscript visually with the addition of 1-2 images showing disease progression.

Author Response

Dear Editor and Reviewers,

I am very grateful for thoughtful comments and recommendations. I wish to express my appreciation for the insightful comments. I have carefully addressed the editor and reviewer’s suggestions and in doing so feel the manuscript is substantially strengthened.

Reviewer #1:

1. Congratulations to the authors for the manuscript. It would be good to support the content of the manuscript visually with the addition of 1-2 images showing disease progression.

Dear reviewer, thank you so much. I really appreciate your kind opinion.

Proper clinical images have been added to the manuscript. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

• All review work is very important for updating purposes. In this case, consider that the importance of the work and its impact on the field needs to be further emphasized.
• Although this is a review, the methodology must be included, i.e., which search engines were used, which years of publication were included, what criteria were used to select the selected articles, etc.
• They do not include the use of eye contour creams (eyelid tightening and redensification).
• Do you consider it important to include the use of Botox?
• It would be important to add Russian-language statistics for each cosmetic or product included in the report. This would give it more relevance.
• You can include a table where you relate each product with the damage it causes and how to prevent that damage.
• When they talk about the serum, they only mention one brand. Why?
• If you leave the suggestions unchanged, it would be worth adding the use of sunscreen.
• The eyebrows are not among the accessory structures of the eye. It would be important to add the function of each structure to the image.
• Reviews must include a summary table of the included works, mentioning at least the author, the type of work and the general results.

Comments on the Quality of English Language

General language review.

Author Response

Dear Editor and Reviewers,

I am very grateful for thoughtful comments and recommendations. I wish to express my appreciation for the insightful comments. I have carefully addressed the editor and reviewer’s suggestions and in doing so feel the manuscript is substantially strengthened.

Reviewer #2:

1. All review work is very important for updating purposes. In this case, consider that the importance of work and its impact on the field needs to be further emphasized.

Dear reviewer, thank you so much for your valuable comments. Your concern has been included.

In an era characterized by the expanding eye cosmetic industry and increasing consumer demand, a comprehensive overview of their ocular side effects is not merely beneficial, but critically important for public health. Alongside consumers, different disciplines, including ophthalmologists, optometrists, dermatologists, and general practitioners should be kept updated. In line with these purposes, this review empowers consumers with evidence-based information to make more informed decisions about the eye cosmetics they use, helping them to avoid potential harm and advocate for their ocular health. Also, it will equip clinicians with a more comprehensive understanding of the diverse ocular presentations associated with eye cosmetic use, leading to faster and more accurate diagnoses. In summary, this report provides a broad range of eye makeup-related side effects and practical recommendations to prevent them. Moreover, by systematically outlining documented side effects, this report provides evidence that can inform stricter guidelines for ingredient safety, product testing, and labeling requirements. For the cosmetic industry, this work underscores the importance of prioritizing product safety and transparent communication, potentially fostering the development of safer formulations.

2. Although this is a review, the methodology must be included, i.e., which search engines were used, which years of publication were included, what criteria were used to select the selected articles, etc.

Dear reviewer, thank you for your comment. The methodology section has been added.

Methodology of Search

A systematic search on PubMed was undertaken to identify relevant articles using the search terms: “cosmetic” OR “makeup” AND “eye” OR “ocular” OR “ophthalmic” OR “eyelash” OR “eyelid” AND “concern” OR “side effect” OR “adverse effect”. Also, the reference list of relevant reports was screened for further results. Non-English publications and those without full-text access were not considered. This search was conducted on February 1, 2025, with no time restriction.

3. They do not include the use of eye contour creams (eyelid tightening and redensification).

Thank you so much; the manuscript has been updated to include points concerning eye contour creams. It is important to highlight that the main focus of this report was to encompass industrial cosmetic products that can be utilized by consumers on their own. Therefore, rejuvenation treatments, which are predominantly conducted in clinic settings, such as laser therapies, non-invasive techniques like Thermage, Botox and filler injections, as well as surgical alternatives like blepharoplasty, were excluded and require a separate thorough review.

Eye Contour Cream

Eye contour cream, commonly referred to as eye cream, is a specialized skincare formulation aimed at addressing issues related to the sensitive skin surrounding the eyes. Eye creams deliver focused hydration to assist in preventing wrinkles and enhancing skin elasticity. Numerous eye creams incorporate components such as caffeine, which can aid in constricting blood vessels and minimizing the visibility of puffiness. Additionally, certain peptides found in some formulations can assist in diminishing dark circles. Furthermore, various eye creams include ingredients like retinol or hyaluronic acid, which can promote collagen production and lessen the appearance of fine lines and wrinkles. Eye creams also serve to shield the skin from environmental stressors and free radicals, factors that can lead to premature aging. Allergic events following eye contour creams are well-documented in the literature. To prevent such side effects, it is recommended to apply a small amount of cream initially, select gentle formulations, and avoid any contact with the eyes.

4. Do you consider it important to include the use of Botox?

Thank you for the comment; it is important to highlight that the main focus of this report was to encompass industrial cosmetic products that can be utilized by consumers on their own. Therefore, rejuvenation treatments, which are predominantly conducted in clinical settings, such as laser therapies, non-invasive techniques like Thermage, Botox and filler injections, as well as surgical alternatives like blepharoplasty, were excluded and require a separate thorough review.

5. It would be important to add Russian-language statistics for each cosmetic or product included in the report. This would give it more relevance.

Dear reviewer, I am disappointed to say that I did not capture your exact meaning in this comment, and I am unclear about the specific statistics you are requesting. If you still feel it is necessary to address this comment, could you please specify the sources you have in mind and provide more clarification? Furthermore, could you indicate the type of Russian-language statistics you consider most relevant, or suggest any particular databases or sources?

6. You can include a table where you relate each product with the damage it causes and how to prevent that damage.

Thank you so much for this comment; Figure 2 has been drawn to address it. Preventive measures are already mentioned in Table 2.

7. When they talk about the serum, they only mention one brand. Why? 

Thank you kindly; that was unintentional. In order to improve generalizability, the brand name has been deleted.

8. If you leave the suggestions unchanged, it would be worth adding the use of sunscreen.

Thank you so much for this comment; as clearly stated in the manuscript, it should be emphasized that the purpose of this report is to focus on the ocular side effects of products which are specific to the eyes. So, the other general formulations, such as primers, concealers, foundations, sunscreen creams and facial masks that can be applied to the eyelids and the periorbital area are not discussed here. However, these products may contain some overlapping ingredients with popular eye cosmetics.

9. The eyebrows are not among the accessory structures of the eye. It would be important to add the function of each structure to the image.

You are completely right; the presence of eyebrow in Figure 1 is to have a prettier picture! Different structures have been defined with a brief description of their functions.

10. Reviews must include a summary table of the works included, mentioning at least the author, the type of work and the general results.

Thanks; done!

11. General language review.

Thank you so much; the manuscript has been entirely checked and edited. 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The work deals with a very interesting and current issue. Certain changes are required before acceptance.
1. The paper discusses potential side effects that are monitored by a dermatologist, whether there are, I think yes, side effects that are also monitored by an ophthalmologist. It should be mentioned somewhere.
2. Consider whether you can also mention permanent eye make-up, which I believe is a serious problem.
3. Can you discuss the important element that the eye preparations are sterile, and that the microbiological correctness is very questionable here, especially during the period of use. That a non-sterile cosmetic product can get into the eye.
4. Are there any data on the side effects of using prostaglandins as Eyelash Growth Serum, bearing in mind that prostaglandin analogues are used topically on the surface of the eye in the treatment of elevated eye pressure and glaucoma?
5. Please discuss the content of heavy metals and side effects in more detail if you find them
6. A large number of cosmetic products for this purpose contain preservatives, discuss how the frequent application of products with preservatives affects the area around the eyes and the eye.

Author Response

Dear Editor and Reviewers,

I am very grateful for thoughtful comments and recommendations. I wish to express my appreciation for the insightful comments. I have carefully addressed the editor and reviewer’s suggestions and in doing so feel the manuscript is substantially strengthened.

Reviewer #3:

The work deals with a very interesting and current issue. Certain changes are required before acceptance.

Dear reviewer, thank you so much for your valuable comments. Your concerns have been addressed.

1. The paper discusses potential side effects that are monitored by a dermatologist, whether there are, I think yes, side effects that are also monitored by an ophthalmologist. It should be mentioned somewhere.

Dear reviewer, thank you for your comment. You are completely right. Your point has been added to the manuscript.

Dermatological evaluations are important for detecting skin reactions to eye cosmetics; however, the unique anatomical and physiological characteristics of the eye necessitate the involvement of ophthalmologists in the observation and management of ocular side effects. Conditions like dry eye disease, infections, chemical injuries, and mechanical damage can adversely affect vision and ocular health. The diagnosis and management of these conditions are the responsibility of an ophthalmologist. Therefore, both dermatological and ophthalmological assessments are vital for a thorough approach to patient care after adverse reactions to eye cosmetics.

2. Consider whether you can also mention permanent eye make-up, which I believe is a serious problem.

Thank you so much; it is important to highlight that the main focus of this report was to encompass industrial cosmetic products that can be utilized by consumers on their own with a transitional or semi-permanent effect. Therefore, permanent eye makeup such as tattoo or even rejuvenation treatments like laser therapies, Botox and filler injections, as well as surgical alternatives (blepharoplasty), were excluded and require a separate thorough review.

3. Can you discuss the important element that the eye preparations are sterile, and that the microbiological correctness is very questionable here, especially during the period of use. That a non-sterile cosmetic product can get into the eye.

Thank you for the comment; your concern has been addressed.

Most eye cosmetic products do not possess true "sterility" in the same strict manner as ophthalmic pharmaceuticals like eye drops, which are typically produced under aseptic conditions and undergo terminal sterilization. Instead, eye cosmetics are generally manufactured to fulfill microbiological cleanliness standards or "low bioburden" requirements. This signifies that manufacturers aim to limit the presence of microorganisms during the production and packaging phases, often through the implementation of good manufacturing practices, the use of preservatives, and comprehensive quality control testing. The goal is to ensure the product is free from harmful levels of pathogenic microorganisms at the time of release. Formulations often include preservative systems designed to inhibit microbial growth. However, the efficacy of these preservatives can be compromised over time or with improper use. Once an eye cosmetic product is opened and used, its sterile (or microbiologically clean) state is immediately compromised due to several factors: repeated contamination from user, direct contact, tears and mucus, finger contamination, environmental exposure, warm and moist environment, and breakdown of preservative systems. The direct consequence of this microbiological contamination is the introduction of a non-sterile product into the delicate ocular environment. This poses significant risks of ocular infection, allergic reaction, and irritation and inflammation. To mitigate these risks, the following instructions are recommended: adhere to period after opening dates (maximum time to use the product once opened), avoid sharing, apply makeup with clean hands, replace after eye infections, avoid adding water or saliva to the products, store products in a cool, dry place away from direct sunlight, and discard products that change in color, odor, or consistency.

4. Are there any data on the side effects of using prostaglandins as Eyelash Growth Serum, bearing in mind that prostaglandin analogues are used topically on the surface of the eye in the treatment of elevated eye pressure and glaucoma?

Thank you for your comment; prostaglandins, whether as anti-glaucoma drops or eyelash growth serums, are associated with a wide range of side effects, shown in Figure 2. Notably, these side effects are occasionally a significant challenge in the management of glaucoma patients, necessitating changing the drops or even discontinuation of topical treatment and opt for surgical management.

5. Please discuss the content of heavy metals and side effects in more detail if you find them.

Thank you so much for this comment; heavy metals pose a real health concern as they are associated with a wide range of side effects, mostly systemic effects such as neurotoxicity, reproductive and developmental issues, cancer risk, and liver and kidney toxicity. Discussing these issues is not fully matched with the title of this work. However, among the ocular side effects, allergic reactions, irritation, and dry eye disease can be pointed out.

While not intentionally added as ingredients, various heavy metals can be present in eye cosmetics as impurities or trace contaminants, primarily stemming from naturally occurring minerals used as pigments or from the manufacturing process. Additionally, several heavy metals have been detected in eye cosmetic formulations, including Lead (Pb), Arsenic (As), Cadmium (Cd), Mercury (Hg), Nickel (Ni), Chromium (Cr), and Cobalt (Co). Their presence, even in small amounts, raises significant health concerns due to their potential for accumulation in the body and their inherent toxicity. The ocular side effects of heavy metals in eye cosmetics can range from immediate irritation to chronic conditions. Contact dermatitis, conjunctivitis, dry eye disease, direct toxicity to the epithelial cells of the cornea and conjunctiva, and pigment deposition are among the ocular side effects linked to the heavy metals found in cosmetics.

6. A large number of cosmetic products for this purpose contain preservatives, discuss how the frequent application of products with preservatives affects the area around the eyes and the eye.

Thank you kindly; your concern has been addressed.

The delicate nature of the periocular skin and the ocular surface makes them particularly vulnerable to the effects of cosmetic preservatives. Many preservatives, particularly BAK, can destabilize the tear film by disrupting its lipid and aqueous layers. This leads to increased tear evaporation, hyperosmolarity, and symptoms characteristic of DED, such as dryness, grittiness, burning, and fluctuating vision. This effect is compounded in individuals with pre-existing dry eye or contact lens wearers. Chronic exposure to preservatives can induce a low-grade inflammatory response on the conjunctiva and cornea. This can lead to cellular damage, loss of goblet cells, and changes in the corneal epithelium, affecting its barrier function. The skin around the eyes is thin and highly permeable, making it susceptible to allergic reactions or irritation from cosmetic ingredients, including preservatives. Symptoms can range from mild redness and itching to more severe swelling, blistering, and eczematous changes. These reactions can occur immediately or develop after prolonged use due to sensitization. Some preservatives, along with other cosmetic ingredients, can obstruct the meibomian gland orifices or be toxic to the meibomian glands themselves. These glands produce the essential lipid component of the tear film, and their dysfunction is a leading cause of evaporative dry eye. While immediate reactions may be mild, the cumulative effect of daily exposure over months or years can lead to more insidious and chronic changes to the ocular surface, even if subclinical. 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

In this review, the author has depicted the side effects of using eye cosmetics and how it can initiate disorders of the ocular surface and its associated structures.

The strengths of this manuscript are as follows.

• The review is comprehensive on pointing out the side effects of using eye cosmetics.
• The review is organized with data and facts.
• The citations are appropriate.

Suggestion: I would strongly suggest incorporating more diagrams, charts, images of adverse effects before and after applying the eye cosmetics into the manuscript. It would grab readers attention more to the awareness that the author wants to portray through this article.

Author Response

Dear Editor and Reviewers,

I am very grateful for thoughtful comments and recommendations. I wish to express my appreciation for the insightful comments. I have carefully addressed the editor and reviewer’s suggestions and in doing so feel the manuscript is substantially strengthened.

Reviewer #4: In this review, the author has depicted the side effects of using eye cosmetics and how it can initiate disorders of the ocular surface and its associated structures. The strengths of this manuscript are as follows. The review is comprehensive, pointing out the side effects of using eye cosmetics. The review is organized with data and facts. The citations are appropriate.

Dear reviewer, thank you so much. I really appreciate your kind opinion.

1. I would strongly suggest incorporating more diagrams, charts, images of adverse effects before and after applying the eye cosmetics into the manuscript. It would grab readers’ attention more to the awareness that the author wants to portray through this article.

Proper figures and clinical images have been added to the manuscript. 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

I believe that all the observations made were adequately addressed, and the work was improved.

The authors added to the methodology that their work is a "Systematic Review." Therefore, by international convention, all such work must include the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart as Figure 1 in the results. To elaborate this, they may refer to a published systematic review. 

An example can be found in: 

Trop. Med. Infect. Dis. 2024, 9, 190. https://doi.org/ 10.3390/tropicalmed9090190 

Comments on the Quality of English Language

Please see Quality of English Language

Author Response

Reviewer #2:

1. I believe that all the observations made were adequately addressed, and the work was improved.

The authors added to the methodology that their work is a "Systematic Review." Therefore, by international convention, all such work must include the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart as Figure 1 in the results. To elaborate this, they may refer to a published systematic review. 

An example can be found in: 

Trop. Med. Infect. Dis. 2024, 9, 190. https://doi.org/ 10.3390/tropicalmed9090190 

Dear reviewer, thank you so much for your valuable comments. I appreciate your constructive comments, which have significantly strengthened my work. It is crucial to highlight that the work is evidently a narrative review, as opposed to a systematic review. In the methodology section, I indicated, "A systematic search on PubMed was undertaken..." to suggest that the search was conducted with thoroughness and discipline. Nevertheless, to avert any misinterpretation, I have modified that phrase.

A meticulous search on PubMed was undertaken to identify relevant articles using the search terms: “cosmetic” OR “makeup” AND “eye” OR “ocular” OR “ophthalmic” OR “eyelash” OR “eyelid” AND “concern” OR “side effect” OR “adverse effect”. Also, the reference lists of relevant reports were screened for further results. The main focus of this report was to encompass industrial cosmetic products (with transient or semi-permanent effects) that can be utilized by consumers on their own. Therefore, rejuvenation treatments, which are predominantly conducted in clinic settings, such as laser therapies, Botox and filler injections, as well as surgical alternatives like blepharoplasty, were excluded. Moreover, non-English publications and those without full-text access were not considered. This search was conducted on February 1, 2025, with no time restriction.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The author has adopted a significant number of comments and I believe that the quality of the work has now improved. I thank you for the excellent cooperation.

Advice for the author - in the following research, when you respond to the reviewer, your answers are very correct, studious and every comment is interpreted. However, indicate where the change was made in the paper based on that comment.

For example You have now made a change for me in 5 out of 6 comments, but I had to look for it in the paper.

Author Response

Reviewer #3:

The author has adopted a significant number of comments, and I believe that the quality of the work has now improved. I thank you for the excellent cooperation.

Advice for the author - in the following research, when you respond to the reviewer, your answers are very correct, studious and every comment is interpreted. However, indicate where the change was made in the paper based on that comment.

For example You have now made a change for me in 5 out of 6 comments, but I had to look for it in the paper.

Dear reviewer, thank you so much for your valuable comments. I appreciate your constructive comments, which have significantly strengthened my work. Thank you so much for your advice; I will certainly consider your point in the future works.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Suggestions for the authors have been well accepted and executed in the manuscript.  

Author Response

Reviewer #4:

Suggestions for the authors have been well accepted and executed in the manuscript.  

Dear reviewer, thank you so much for your valuable comments. I appreciate your constructive comments, which have significantly strengthened my work.

Author Response File: Author Response.pdf