International Journal of Molecular Sciences

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11 pages, 5570 KiB

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Transmembrane Mucin Response in Conjunctival Epithelial Cells Exposed to Wall Shear Stresses

by Shir Itah, David Elad, Ariel J. Jaffa, Dan Grisaru and Mordechai Rosner

Int. J. Mol. Sci. 2023, 24(7), 6589; https://doi.org/10.3390/ijms24076589 - 01 Apr 2023

Viewed by 1235

Abstract

Human conjunctival epithelium cells (HCEC) line the inner surface of the eyelid and cover the sclera and are continuously subjected to wall shear stresses (WSS). The effects of external forces on the conjunctival epithelium are not fully known. The conjunctival epithelium contains stratified [...] Read more.

Human conjunctival epithelium cells (HCEC) line the inner surface of the eyelid and cover the sclera and are continuously subjected to wall shear stresses (WSS). The effects of external forces on the conjunctival epithelium are not fully known. The conjunctival epithelium contains stratified squamous cells that synthesize the membrane-spanning mucins MUC1 and MUC16, which play important roles in protecting the ocular surface. Alterations in both gel-forming and membrane-tethered mucins occur in drying ocular surface diseases. The aim of this study was to explore the mechanobiological characteristics of transmembrane mucin secretion and cellular alterations of primary HCEC exposed to airflow-induced WSS perturbations. We exposed the HCEC to a steady WSS of 0.5 dyne/cm² for durations of 15 and 30 min. Cytoskeletal alterations and MUC1 secretions were studied using immunohistochemically fluorescent staining with specific antibodies. We investigated for the first time an in vitro model of membrane-tethered mucin secretion by HCEC in response to WSS. The exposure of HCEC to WSS increased the polymerization of F-actin, altered the cytoskeletal shape and reduced the secretion of membrane-tethered MUC1. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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11 pages, 2614 KiB

Open AccessArticle

Assessment of Laser Parameters to Improve Lid Tension—A Proof of Concept towards Lasercanthoplasty

by Christoph Holtmann, Joana Witt, Alexandra Schilcher, Amar Avdakovic, Alessa Hutfilz, Dirk Theisen-Kunde, Katharina Wiebe-Ben Zakour, Erich Knop and Gerd Geerling

Int. J. Mol. Sci. 2023, 24(5), 4757; https://doi.org/10.3390/ijms24054757 - 01 Mar 2023

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Abstract

Background: Preliminary clinical work indicates that increasing eyelid tension improves the function of the meibomian glands. The aim of this study was to optimize laser parameters for a minimally invasive laser treatment to increase eyelid tension by coagulation of the lateral tarsal plate [...] Read more.

Background: Preliminary clinical work indicates that increasing eyelid tension improves the function of the meibomian glands. The aim of this study was to optimize laser parameters for a minimally invasive laser treatment to increase eyelid tension by coagulation of the lateral tarsal plate and canthus. Methods: Experiments were performed on a total of 24 porcine lower lids post mortem, with six lids in each group. Three groups were irradiated with an infrared B radiation laser. Laser-induced lower eyelid shortening was measured and the increase in eyelid tension was assessed with a force sensor. A histology was performed to evaluate coagulation size and laser-induced tissue damage. Results: In all three groups, a significant shortening of the eyelids after irradiation was noticed (p < 0.0001). The strongest effect was seen with 1940 nm/1 W/5 s, showing −15.1 ± 3.7% and −2.5 ± 0.6 mm lid shortening. The largest significant increase in eyelid tension was seen after placing the third coagulation. Conclusion: Laser coagulation leads to lower eyelid shortening and an increase in lower eyelid tension. The strongest effect with the least tissue damage was shown for laser parameters of 1470 nm/2.5 W/2 s. In vivo studies of this effect have to confirm the efficacy of this concept prior to clinical application. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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23 pages, 4523 KiB

Open AccessArticle

Development of In Vitro Dry Eye Models to Study Proliferative and Anti-Inflammatory Effects of Allogeneic Serum Eye Drops

by Silja Voß, Till Behrmann and Stephan Reichl

Int. J. Mol. Sci. 2023, 24(2), 1567; https://doi.org/10.3390/ijms24021567 - 13 Jan 2023

Cited by 2 | Viewed by 2672

Abstract

This study aimed to develop valid in vitro models for preclinical evaluation of proliferative and anti-inflammatory effects of human allogeneic serum eye drops for dry eye disease (DED) treatment. A DED wound healing model was developed by analyzing the influence of coating and [...] Read more.

This study aimed to develop valid in vitro models for preclinical evaluation of proliferative and anti-inflammatory effects of human allogeneic serum eye drops for dry eye disease (DED) treatment. A DED wound healing model was developed by analyzing the influence of coating and serum concentrations on human corneal epithelial (HCE-T) wound closure. Further, intralaboratory variance, freeze–thaw cycle effects, donor variability and stability assays were conducted. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were used to induce the gene expression of matrix metalloproteinase 9 (MMP9), cyclooxygenase 2 (COX2), transforming growth factor-β (TGFβ) and IL-1β. MMP9 induction was optimized using a design-of-experiments (DoE) approach and applied to examine serum under static and dynamic conditions. MMP9 protein expression was analyzed by ELISA. The DED wound healing model detected proliferative effects of serum down to 1% with a small intralaboratory variance. Serum stability was shown over six months, donor variance could be detected, and freeze–thaw cycle effects did not affect wound closure. Serum decreased MMP9 expression on the gene and protein levels. The induction method was successfully optimized using DoE modeling and transferred to a dynamic setting mimicking tear film fluidics. The DED wound healing and inflammatory DED model present useful in vitro models for the preclinical evaluation of allogeneic serum eye drops without the use of animal experiments. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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10 pages, 2004 KiB

Open AccessArticle

The Effects of Fisetin on Cyclosporine-Treated Dry Eye Disease in Dogs

by Kristína Krajčíková, Agnieszka Balicka, Mária Lapšanská, Alexandra Trbolová, Zuzana Guľašová, Daria Kondrakhova, Vladimír Komanický, Adriana Rašiová and Vladimíra Tomečková

Int. J. Mol. Sci. 2023, 24(2), 1488; https://doi.org/10.3390/ijms24021488 - 12 Jan 2023

Viewed by 1976

Abstract

Dry eye disease (DED) is a chronic debilitating ophthalmological disease with the current therapeutic options focused on the suppression of the symptoms. Among the possibilities of how to improve DED therapy, polyphenols have shown an enormous capacity to counteract DED functional changes. The [...] Read more.

Dry eye disease (DED) is a chronic debilitating ophthalmological disease with the current therapeutic options focused on the suppression of the symptoms. Among the possibilities of how to improve DED therapy, polyphenols have shown an enormous capacity to counteract DED functional changes. The study aimed to specifically target pathophysiological mechanisms by the addition of fisetin to the cyclosporine treatment protocol. We examined dog patients with DED on cyclosporine treatment that were administered 0.1% fisetin or fisetin-free eye drops. For the assessment of fisetin effects, tear film production and matrix metalloproteinase 9 (MMP-9) were studied in the tear film. Tear production was not recovered after 7 or 14 days (9.40 mm ± 6.02 mm, p = 0.47; 9.80 mm ± 6.83 mm, p = 0.53, respectively). MMP-9 levels significantly increased after 7 days and then dropped after 14 days (775.44 ng/mL ± 527.52 ng/mL, p = 0.05; 328.49 ng/mL ± 376.29 ng/mL, p = 1.00, respectively). Fisetin addition to cyclosporine DED treatment was not able to restore tear fluid production but influenced molecular pathological events through MMP-9. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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11 pages, 1229 KiB

Open AccessArticle

The Effect of Mesenchymal Stem Cells on Dry Eye in Sjogren Syndrome Mouse Model

by Soojung Shin, Seul-Gi Yoon, Miso Kim, Eun Jeong Cheon, Youngseo Jeon, Hyun Jung Lee and So-Hyang Chung

Int. J. Mol. Sci. 2023, 24(2), 1039; https://doi.org/10.3390/ijms24021039 - 05 Jan 2023

Cited by 3 | Viewed by 1865

Abstract

Sjögren’s syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study [...] Read more.

Sjögren’s syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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16 pages, 471 KiB

Open AccessArticle

0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial

by Gabriel Sosne, Hynda K. Kleinman, Clark Springs, Robert Hollis Gross, Jihye Sung and Shinwook Kang

Int. J. Mol. Sci. 2023, 24(1), 554; https://doi.org/10.3390/ijms24010554 - 29 Dec 2022

Cited by 2 | Viewed by 2999

Abstract

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of [...] Read more.

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan–Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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13 pages, 3959 KiB

Open AccessArticle

Impact of High Glucose on Ocular Surface Glycocalyx Components: Implications for Diabetes-Associated Ocular Surface Damage

by Judy Weng, Steven Trinh, Rachel Lee, Rana Metwale and Ajay Sharma

Int. J. Mol. Sci. 2022, 23(22), 14289; https://doi.org/10.3390/ijms232214289 - 18 Nov 2022

Cited by 2 | Viewed by 1896

Abstract

Diabetes mellitus causes several detrimental effects on the ocular surface, including compromised barrier function and an increased risk of infections. The glycocalyx plays a vital role in barrier function. The present study was designed to test the effect of a high glucose level [...] Read more.

Diabetes mellitus causes several detrimental effects on the ocular surface, including compromised barrier function and an increased risk of infections. The glycocalyx plays a vital role in barrier function. The present study was designed to test the effect of a high glucose level on components of glycocalyx. Stratified human corneal and conjunctival epithelial cells were exposed to a high glucose concentration for 24 and 72 h. Changes in Mucin (MUC) 1, 4, 16 expression were quantified using real-time PCR and ELISA. Rose bengal and jacalin staining were used to assess the spatial distribution of MUC16 and O-glycosylation. Changes in the gene expression of five glycosyltransferases and forty-two proteins involved in cell proliferation and the cell cycle were also quantified using PCR and a gene array. High glucose exposure did not affect the level or spatial distribution of membrane-tethered MUC 1, 4, and 16 either in the corneal or conjunctival epithelial cells. No change in gene expression in glycosyltransferases was observed, but a decrease in the gene expression of proteins involved in cell proliferation and the cell cycle was observed. A high-glucose-mediated decrease in gene expression of proteins involved in cellular proliferation of corneal and conjunctival epithelial cells may be one of the mechanisms underlying a diabetes-associated decrease in ocular surface’s glycocalyx. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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16 pages, 2284 KiB

Open AccessArticle

Immunomodulatory Effect of Human Lactoferrin on Toll-like Receptors 2 Expression as Therapeutic Approach for Keratoconus

by Uxía Regueiro, Maite López-López, Rubén Varela-Fernández, Tomás Sobrino, Elio Diez-Feijoo and Isabel Lema

Int. J. Mol. Sci. 2022, 23(20), 12350; https://doi.org/10.3390/ijms232012350 - 15 Oct 2022

Cited by 4 | Viewed by 1888

Abstract

Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the [...] Read more.

Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the door to future therapies. In this prospective clinical study, serum and tear LTF concentrations were quantified in 90 KC patients and 60 controls. A correlation analysis with multiple blood and tear immunoinflammatory mediators, and KC-associated tomographic parameters, was performed. An in vitro study using HEK-Blue^TMhTLR2 cell cultures was also conducted to determine the expression and functionality of TLR2 under the influence of LTF treatment. As a result, a LTF decreased was observed in KC patients compared to controls (p < 0.0001), evidencing the strong correlation with TLR2 overexpression at systemic and ocular surface level, with inflammatory mediator upregulation and with KC severity. In stimulated cell cultures, TLR2 expression was decreased using 2 mg/mL of LTF. The levels of secreted embryonic alkaline phosphatase (SEAP) and interleukin-8 (IL-8) were also reduced in supernatants after LTF treatment. As conclusions, the dysregulation of LTF and TLR2 in the ocular surface of KC patients contributes to KC severity by maintaining a detrimental chronic immune–inflammatory state. The immunomodulatory properties of LTF on TLR2 expression suggest its potential as a therapeutic approach for KC. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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11 pages, 1002 KiB

Open AccessArticle

The Diagnostic Value of MRI-Based Radiomic Analysis of Lacrimal Glands in Patients with Sjögren’s Syndrome

by Delia Doris Muntean, Maria Bădărînză, Paul Andrei Ștefan, Manuela Lavinia Lenghel, Georgeta Mihaela Rusu, Csaba Csutak, Paul Alexandru Coroian, Roxana Adelina Lupean and Daniela Fodor

Int. J. Mol. Sci. 2022, 23(17), 10051; https://doi.org/10.3390/ijms231710051 - 02 Sep 2022

Cited by 8 | Viewed by 2259

Abstract

This study aimed to assess the effectiveness of MRI-based texture features of the lacrimal glands (LG) in augmenting the imaging differentiation between primary Sjögren’s Syndrome (pSS) affected LG and healthy LG, as well as to emphasize the possible importance of radiomics in pSS [...] Read more.

This study aimed to assess the effectiveness of MRI-based texture features of the lacrimal glands (LG) in augmenting the imaging differentiation between primary Sjögren’s Syndrome (pSS) affected LG and healthy LG, as well as to emphasize the possible importance of radiomics in pSS early-imaging diagnosis. The MRI examinations of 23 patients diagnosed with pSS and 23 healthy controls were retrospectively included. Texture features of both LG were extracted from a coronal post-contrast T1-weighted sequence, using a dedicated software. The ability of texture features to discriminate between healthy and pSS lacrimal glands was performed through univariate, multivariate, and receiver operating characteristics analysis. Two quantitative textural analysis features, RunLengthNonUniformityNormalized (RLNonUN) and Maximum2DDiameterColumn (Max2DDC), were independent predictors of pSS-affected glands (p < 0.001). Their combined ability was able to identify pSS LG with 91.67% sensitivity and 83.33% specificity. MRI-based texture features have the potential to function as quantitative additional criteria that could increase the diagnostic accuracy of pSS-affected LG. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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Review

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18 pages, 609 KiB

Open AccessReview

Impact of Microplastics on the Ocular Surface

by Duoduo Wu, Blanche X. H. Lim, Ivan Seah, Shay Xie, Julia E. Jaeger, Robert K. Symons, Amy L. Heffernan, Emily E. M. Curren, Sandric C. Y. Leong, Andri K. Riau, Dawn K. A. Lim, Fiona Stapleton, Mohammad Javed Ali, Swati Singh, Louis Tong, Jodhbir S. Mehta, Xinyi Su and Chris H. L. Lim

Int. J. Mol. Sci. 2023, 24(4), 3928; https://doi.org/10.3390/ijms24043928 - 15 Feb 2023

Cited by 2 | Viewed by 3249

Abstract

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the [...] Read more.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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25 pages, 1683 KiB

Open AccessReview

An Overview of the Dry Eye Disease in Sjögren’s Syndrome Using Our Current Molecular Understanding

by Kevin Y. Wu, Merve Kulbay, Cristina Tanasescu, Belinda Jiao, Bich H. Nguyen and Simon D. Tran

Int. J. Mol. Sci. 2023, 24(2), 1580; https://doi.org/10.3390/ijms24021580 - 13 Jan 2023

Cited by 10 | Viewed by 4588

Abstract

Sjögren’s syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and [...] Read more.

Sjögren’s syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren’s syndrome dry eye (SSDE) from non-Sjögren’s syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren’s syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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16 pages, 328 KiB

Open AccessReview

Dry Eye Disease: What Is the Role of Vitamin D?

by Maurizio Rolando and Stefano Barabino

Int. J. Mol. Sci. 2023, 24(2), 1458; https://doi.org/10.3390/ijms24021458 - 11 Jan 2023

Cited by 8 | Viewed by 6415

Abstract

Dry eye disease (DED) is a multifactorial condition resulting from reduced tear secretion from the lacrimal glands, increased tear water evaporation or the production of poor-quality tears. Such tear instability can lead to inflammation and damage of the ocular surface, as well as [...] Read more.

Dry eye disease (DED) is a multifactorial condition resulting from reduced tear secretion from the lacrimal glands, increased tear water evaporation or the production of poor-quality tears. Such tear instability can lead to inflammation and damage of the ocular surface, as well as to abnormal nociception. Historically, tear substitutes and corticosteroids have been the bastion of DED therapy, but a substantial number of patients still suffer from residual symptoms even after being treated with traditional treatments. Aiming to find safe and effective alternative therapies, recent efforts have been focused on the role of vitamin D in the cellular physiology of the eye. Possibly because of its positive effect in modulating the immune and inflammatory responses, the systemic supplementation of vitamin D seems, indeed, to be an effective therapeutic strategy, especially, but not only, for patients affected by DED that does not respond to conventional treatments. In this context, this review focuses on the literature reporting on the pathogenesis and treatment of DED, with a special emphasis on the recent investigations reporting on the potential role of the systemic administration of vitamin D as a therapeutic approach in the management of such condition. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

24 pages, 1224 KiB

Open AccessReview

The Management of Ocular Surface Squamous Neoplasia (OSSN)

by Clarice H. Y. Yeoh, Jerome J. R. Lee, Blanche X. H. Lim, Gangadhara Sundar, Jodhbir S. Mehta, Anita S. Y. Chan, Dawn K. A. Lim, Stephanie L. Watson, Santosh G. Honavar, Ray Manotosh and Chris H. L. Lim

Int. J. Mol. Sci. 2023, 24(1), 713; https://doi.org/10.3390/ijms24010713 - 31 Dec 2022

Cited by 6 | Viewed by 4818

Abstract

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus [...] Read more.

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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20 pages, 787 KiB

Open AccessReview

Topical Omega-3 Fatty Acids Eyedrops in the Treatment of Dry Eye and Ocular Surface Disease: A Systematic Review

by Benjamin Paik and Louis Tong

Int. J. Mol. Sci. 2022, 23(21), 13156; https://doi.org/10.3390/ijms232113156 - 29 Oct 2022

Cited by 3 | Viewed by 2857

Abstract

Dry eye is a common inflammatory condition of the ocular surface. While oral omega-3 supplementation for its treatment has been extensively studied, recent large-scale studies have cast doubt on their efficacy. However, efficacy of topical omega-3 has yet to be reviewed. We performed [...] Read more.

Dry eye is a common inflammatory condition of the ocular surface. While oral omega-3 supplementation for its treatment has been extensively studied, recent large-scale studies have cast doubt on their efficacy. However, efficacy of topical omega-3 has yet to be reviewed. We performed a systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating topical omega-3 in dry eye. Five human and five animal studies were included. Of the five human studies, two were on dry eye disease (DED), one was on contact lens discomfort, and two were on patients undergoing corneal collagen crosslinking. In humans, there is promising evidence for improved ocular surface staining and tear break-up time compared to controls, equivocal evidence for improvements to ocular surface symptoms and meibomian gland dysfunction, and no effect on increasing tear production. Data from animal models largely agree with these findings, and further reveal decreased inflammatory cytokines and monocyte infiltration. Our review suggests that topical omega-3 is a promising treatment for dry eye, but also points to the paucity of evidence in this field. Further trials in humans are required to characterize effects of topical omega-3 and optimize its dosage. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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Other

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17 pages, 4665 KiB

Open AccessCase Report

Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review

by Hiroshi Toshida, Tomoto Kasahara, Masamichi Kiriyama, Yuma Iwasaki, Jobu Sugita, Kohei Ichikawa, Toshihiko Ohta and Katsumi Miyahara

Int. J. Mol. Sci. 2023, 24(10), 8926; https://doi.org/10.3390/ijms24108926 - 18 May 2023

Cited by 2 | Viewed by 1528

Abstract

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural^®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first [...] Read more.

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural^®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural^®. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural^® can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted. Full article

(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders 4.0)

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