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Advances in Dry Eye Disease Treatment
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Advances in Dry Eye Disease Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 47235

Special Issue Editors

Dr. Piera Versura

E-Mail Website
Collection Editor
Ocular Surface and Translational Research Lab, Ophthalmology Unit, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy
Interests: dry eye disease; ocular surface disorders; diagnostic biomarkers; microfluidic assay; in vitro & in vivo experimental models; lactoferrin
Special Issues, Collections and Topics in MDPI journals
Dr. Murat Dogru

E-Mail Website
Collection Editor
1. Department of Ophthalmology, Keio University School of Medicine, Shi-nanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan
2. Visiting Senior Fellow, UNSW School of Optometry and Vision Science, Sydney, NSW 2052, Australia
Interests: dry eye; oxidative stress; diagnostic imaging; biomarkers; ocular allergy; contact lens
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is recognized that the prevalence of dry eye disease is rapidly increasing, as is its burden, with an associated important need for research into new therapeutics. Conventional dry eye treatments include over-the-counter products such as tear substitutes, warm compresses, lid hygiene shampoo or ocular gauzes. Clinicians now have several other choices for patients who are unresponsive to traditional therapies, or suffering from severely dry eyes, including topical medications, blood-derived products, and different types of energy delivery devices.

This Topical Collection aims to collect contributions from distinguished authors who actively experience, in their own experimental and clinical work, the most innovative options for dry eye disease.

Dr. Piera Versura
Dr. Murat Dogru
Collection Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dry eye disease
  • meibomian gland
  • tear substitutes
  • corticosteroids
  • cyclosporin
  • antibiotics
  • non steroid anti-inflammatory drugs
  • biological tear substitutes
  • nutrients
  • pulsed light

Published Papers (20 papers)

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11 pages, 812 KiB  
Article
Tear Film Stabilization and Symptom Improvement in Dry Eye Disease: The Role of Hyaluronic Acid and Trehalose Eyedrops versus Carmellose Sodium
by José-María Sánchez-González, Carmen Silva-Viguera, María Carmen Sánchez-González, Raúl Capote-Puente, Concepción De-Hita-Cantalejo, Antonio Ballesteros-Sánchez, Lydia Ballesteros-Durán, Marta-C. García-Romera and Estanislao Gutiérrez-Sánchez
J. Clin. Med. 2023, 12(20), 6647; https://doi.org/10.3390/jcm12206647 - 20 Oct 2023
Viewed by 941
Abstract
This study evaluated the effectiveness of hyaluronic acid and trehalose (HA/trehalose) eyedrops in managing dry eye disease (DED) symptoms by measuring tear stability and administering a DED questionnaire. Sixty patients were treated with either HA/trehalose eyedrops (Tear A) or carmellose sodium eyedrops (Tear [...] Read more.
This study evaluated the effectiveness of hyaluronic acid and trehalose (HA/trehalose) eyedrops in managing dry eye disease (DED) symptoms by measuring tear stability and administering a DED questionnaire. Sixty patients were treated with either HA/trehalose eyedrops (Tear A) or carmellose sodium eyedrops (Tear B) as controls. The tear breakup time (TBUT) and non-invasive breakup time (NIBUT) were monitored, and patients completed the standard patient evaluation of eye dryness (SPEED) questionnaire. After two months of twice-daily applications, patients treated with the HA/trehalose eyedrops demonstrated significant improvements in the NIBUT (12.98 ± 3.22 s) and TBUT (12.95 ± 2.98 s), indicating increased tear stability. Moreover, they reported lower dry eye sensation (6.70 ± 4.94 SPEED score points), suggesting a reduction in DED symptoms. These findings underscore the efficacy of HA/trehalose eyedrops in improving both the objective and subjective signs of DED, with twice-daily application enhancing ocular surface conditions and reducing patient-reported symptoms. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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8 pages, 497 KiB  
Article
Effectiveness and Adherence of Dry Eye Patients Who Switched from Short- to Long-Acting Diquafosol Ophthalmic Solution
by Sho Ishikawa, Takanori Sasaki, Takahumi Maruyama, Koichiro Murayama and Kei Shinoda
J. Clin. Med. 2023, 12(13), 4495; https://doi.org/10.3390/jcm12134495 - 05 Jul 2023
Cited by 1 | Viewed by 1166
Abstract
Long-acting (lasting extend) diquafosol ophthalmic solution 3% (DQSLX) is administered three times daily versus six times daily for the currently approved diquafosol ophthalmic solution (DQS). We investigated the efficacy and adherence of switching from DQS to DQSLX in patients with dry eye disease. [...] Read more.
Long-acting (lasting extend) diquafosol ophthalmic solution 3% (DQSLX) is administered three times daily versus six times daily for the currently approved diquafosol ophthalmic solution (DQS). We investigated the efficacy and adherence of switching from DQS to DQSLX in patients with dry eye disease. We retrospectively enrolled 54 patients (17 men and 37 women) with eye drop prescription changes from DQS to DQSLX between December 2022 and March 2023. The number of eye drops, subjective symptoms, tear breakup time (TBUT), and fluorescein staining scores from baseline to 4 weeks after starting DQSLX were evaluated. Participants then chose between DQSLX and DQS. Patients administered DQSLX three times per day, as listed on the package insert, 88.9% of the time; significantly higher than the 5.6% of patients who used DQS six times per day, as instructed. The DQSLX group showed significant improvements in symptoms and fluorescein staining scores (23.3 ± 20.1 and 0.8 ± 1.7, respectively) compared with the baseline (37.8 ± 24.1 and 1.1 ± 1.5, p = 0.01 and <0.001, respectively). The TBUT in the DQSLX group (5.0 ± 2.5 s) did not significantly improve compared to the DQS group (4.5 ± 1.7 s) (p = 0.75). Fifty-one (94.4%) patients opted to continue DQSLX because of the pleasant feeling of the eye drops, long-lasting moisture, and less frequent administration. The efficacy and adherence of DQSLX was comparable to DQS. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 2232 KiB  
Article
The Effect of High Molecular Weight Hyaluronic Acid and Latanoprost Eyedrops on Tear Functions and Ocular Surface Status in C57/BL6 Mice
by Murat Dogru, Takashi Kojima, Kazunari Higa, Ayako Igarashi, Haruka Kudo, Wolfgang G. K. Müller-Lierheim, Kazuo Tsubota and Kazuno Negishi
J. Clin. Med. 2023, 12(2), 544; https://doi.org/10.3390/jcm12020544 - 09 Jan 2023
Cited by 1 | Viewed by 1437
Abstract
Anti-glaucoma eye drop treatment often induces ocular surface problems, including dry eyes, and may be associated with poor medication compliance. This study aimed to investigate the effects of a novel high molecular weight hyaluronic acid and Latanoprost eye drop on intraocular pressure, as [...] Read more.
Anti-glaucoma eye drop treatment often induces ocular surface problems, including dry eyes, and may be associated with poor medication compliance. This study aimed to investigate the effects of a novel high molecular weight hyaluronic acid and Latanoprost eye drop on intraocular pressure, as well as the tear function and ocular surface alterations in wild type mice, comparing the results with the mice receiving commercially available Latanoprost eye drops and mice receiving no treatment. The mice were divided into three groups: Group I, control group (no treatment group); Group II, commercial Latanoprost eye drop (LP); and Group III, Comfort Shield (CS) + Latanoprost (LP) eye drop (CS + LP). The CS + LP eye drop group had an IOP lowering effect comparable to the commercial LP eye drop group. The mice receiving LP eye drops had significantly worse corneal staining scores, lesser goblet cell density(GCD), higher numbers of CD45+ staining cells, significantly higher tear film concentrations of IL-6 and IL1-b, and a significantly lower expression of corneal ZO-1 mRNA compared with the mice receiving CS + LP 7 days after eye drop instillations (p < 0.05). In conclusion, the new CS + LP formulation appeared to induce less inflammation, less corneal vital staining, and a better barrier status with an IOP lowering effect comparable to the commercial LP eye drops. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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17 pages, 2486 KiB  
Article
Olive Pomace Phenolic Compounds: From an Agro-Industrial By-Product to a Promising Ocular Surface Protection for Dry Eye Disease
by Nikolaos Katsinas, Uta Gehlsen, Laura García-Posadas, Soraya Rodríguez-Rojo, Philipp Steven, María J. González-García and Amalia Enríquez-de-Salamanca
J. Clin. Med. 2022, 11(16), 4703; https://doi.org/10.3390/jcm11164703 - 11 Aug 2022
Cited by 3 | Viewed by 2993
Abstract
Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil industry, is rich in high-value polyphenols. Their anti-inflammatory and immunomodulatory activities were determined on human CD4+ T cells (hTCD4+) [...] Read more.
Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil industry, is rich in high-value polyphenols. Their anti-inflammatory and immunomodulatory activities were determined on human CD4+ T cells (hTCD4+) and in a DED animal model. The viability of hTCD4+ cells isolated from peripheral blood and activated with phytohemagglutinin-M was evaluated after treatment for 48 h with an olive pomace extract (OPT3, 0.10–0.40 mg/mL) and its major compound, hydroxytyrosol (25–100 μM). Regarding the DED animal model, 100 μM hydroxytyrosol, 0.20 mg/mL OPT3, or vehicle (borate buffer) were topically administered to 14 days-desiccating stress-exposed (constant airflow/scopolamine administration) C57BL/6 mice. Tear volume, corneal fluorescein staining (CFS), CD4+, and CD8+ T cell count in lymph nodes (flow cytometry), and IP-10 and TNF-α gene expression (qRT-PCR) in the cornea, conjunctiva, and lacrimal glands were evaluated. OPT3 (0.2–0.4 mg/mL) and hydroxytyrosol (100 μM) significantly reduced hTCD4+ proliferation. In mice, both treatments reduced lacrimal gland IP-10 gene expression. OPT3 also decreased CFS, and conjunctival IP-10 and corneal TNF-α gene expression. In lymph nodes, hydroxytyrosol reduced CD3+, OPT3, and CD8+ count. Thus, a high-value application as a promising DED protection was proposed for olive pomace. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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12 pages, 1755 KiB  
Article
Hyaluronic Acid and Galacto-Xyloglucan Eyedrop Efficacy in Young-Adult Oral Contraceptive Users of Childbearing Age
by José-María Sánchez-González, Concepción De-Hita-Cantalejo and María Carmen Sánchez-González
J. Clin. Med. 2022, 11(15), 4458; https://doi.org/10.3390/jcm11154458 - 30 Jul 2022
Cited by 2 | Viewed by 1466
Abstract
To assess the efficacy of 0.4% hyaluronic acid and 0.2% galacto-xyloglucan for the subjective symptoms of dry eye disease and tear film invasive and noninvasive signs in 34 young-adult oral contraceptive users of childbearing age, a prospective, longitudinal, single-blind, clinical study was performed [...] Read more.
To assess the efficacy of 0.4% hyaluronic acid and 0.2% galacto-xyloglucan for the subjective symptoms of dry eye disease and tear film invasive and noninvasive signs in 34 young-adult oral contraceptive users of childbearing age, a prospective, longitudinal, single-blind, clinical study was performed in a population of childbearing-age oral-contraceptive consumers. Subjective dry eye disease questionnaires, and invasive and noninvasive tear film assessments were reported before and after six weeks of hyaluronic acid with galacto-xyloglucan (HA-GX) treatment versus hyaluronic acid alone (HA). HA-GX treatment resulted in a greater decrease in the ocular surface disease index (17.01 ± 11.36 score points, p < 0.01) than the HA variation (11.61 ± 11.18 score points, p < 0.01). The standard patient evaluation of eye dryness also decreased more in the HA-GX group (4.06 ± 5.50 score points, p < 0.01) than in the HA alone group (0.70 ± 3.16, p = 0.21). Regarding noninvasive break-up time (NIBUT), the HA-GX group’s first NIBUT achieved an increase of 1.75 ± 1.16 s, p < 0.01, while the HA-alone group increased by only 0.54 ± 1.01 s, p < 0.01. The HA-GX group’s mean NIBUT reported an increase of 3.72 ± 5.69 s, p < 0.01; however, the HA-alone group achieved 2.19 ± 5.26 s, p = 0.05. Hyaluronic acid in combination with galacto-xyloglucan significantly decreased subjective dry eye disease symptoms and increased first and mean NIBUT compared to hyaluronic acid alone. Galacto-xyloglucan added efficacy in young-adult childbearing-age oral contraceptive users. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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9 pages, 2026 KiB  
Article
Aberrant Corneal Homeostasis in Neurosurgery-Induced Neurotrophic Keratopathy
by Shimpei Oba, Kaoru Araki-Sasaki, Tomoyuki Chihara, Takashi Kojima, Dogru Murat and Kanji Takahashi
J. Clin. Med. 2022, 11(13), 3804; https://doi.org/10.3390/jcm11133804 - 30 Jun 2022
Cited by 1 | Viewed by 1456
Abstract
The characteristic features of neurotrophic keratopathy have been well documented by in vivo and in vitro studies using animal models. However, case reports of neurotrophic keratopathy induced by neurosurgery are limited. We describe the clinical characteristics, anterior segment optical coherence tomography (AS-OCT) and [...] Read more.
The characteristic features of neurotrophic keratopathy have been well documented by in vivo and in vitro studies using animal models. However, case reports of neurotrophic keratopathy induced by neurosurgery are limited. We describe the clinical characteristics, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) findings of neurotrophic keratopathy induced by surgery for intracranial lesions. This is a case series including 6 eyes of 3 patients (mean age, 69.67 ± 12.50 years) with unilateral neurotrophic keratopathy. The clinical findings of three patients were described and IVCM findings of three patients were analyzed. The duration of neuropathy ranged from 2 to 30 years (median, 22 years). Thickening of the epithelial layer and higher reflection density of the anterior stroma were observed during the healing process using AS-OCT. The mean nerve fiber density of the subepithelial plexus, as determined by IVCM, was 1943 ± 1000 μm/mm2 for neurotrophic eyes and 2242 ± 600.3 μm/mm2 for contralateral eyes (p = 0.0347). The mean respective dendritic cell densities were 30.8 ± 21.8 and 6.25 ± 5.59 cells/mm2 (p < 0.0001), while the mean basal cell sizes were 259 ± 86.5 and 185 ± 45.9 μm2 (p < 0.0001), respectively. These findings suggest that neurosurgery-induced neurotrophic keratopathy may be associated with alterations in the healing process and immune cell distribution in the cornea. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 2217 KiB  
Article
Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer
by José-María Sánchez-González, Concepción De-Hita-Cantalejo, Concepción Martínez-Lara and María Carmen Sánchez-González
J. Clin. Med. 2022, 11(13), 3719; https://doi.org/10.3390/jcm11133719 - 27 Jun 2022
Cited by 3 | Viewed by 1784
Abstract
To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with [...] Read more.
To evaluate the stability and permanence of the liquid film created after the instillation of 0.15% crosslinked hyaluronic acid with liposomes and crocin versus the effect of 0.15% standard hyaluronic acid, a prospective, longitudinal, single-blind, single-center study was conducted in symptomatic populations with a novel noninvasive ocular surface analyzer. Limbal and bulbar redness classification, lipid layer thickness, tear meniscus height, and first and mean noninvasive break-up time (FNIBUT and MNIBUT) were performed before and 30 and 45 min after liposome-crosslinked hyaluronic acid (LCHA) and standard hyaluronic acid (HA) eye drop instillations. LCHA had a higher lipid layer thickness than HA (grades 2.00 ± 0.83 and 1.17 ± 0.63 on the Guillon pattern, respectively). LCHA achieved a better tear meniscus height than HA (0.23 ± 0.02 and 0.21 ± 0.02 mm, respectively). LCHA improved FNIBUT and MNIBUT more than HA (for FNIBUT, 6.30 ± 0.94 and 4.77 ± 0.89 s, respectively. For MNIBUT, 17.23 ± 5.11 and 12.41 ± 4.18 s, respectively). Crosslinking hyaluronic acid with liposomes and crocin significantly increases the permanence and stability of the lipid, aqueous, and mucin tear film layers. In a short-term period, liposome and crosslinked hyaluronic acid achieved better first and mean noninvasive break-up times than standard hyaluronic acid. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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17 pages, 2787 KiB  
Article
Contact Lenses Loaded with Melatonin Analogs: A Promising Therapeutic Tool against Dry Eye Disease
by Francisco Javier Navarro-Gil, Fernando Huete-Toral, Carmen Olalla Domínguez-Godínez, Gonzalo Carracedo and Almudena Crooke
J. Clin. Med. 2022, 11(12), 3483; https://doi.org/10.3390/jcm11123483 - 17 Jun 2022
Cited by 8 | Viewed by 1939
Abstract
Melatonin analogs topically administered evoke a potent tear secretagogue effect in rabbits. This route of drug administration requires high drug concentration and frequent dosing due to its reduced ocular surface retention. Therefore, contact lenses (CLs) have emerged as an alternative drug-delivery system that [...] Read more.
Melatonin analogs topically administered evoke a potent tear secretagogue effect in rabbits. This route of drug administration requires high drug concentration and frequent dosing due to its reduced ocular surface retention. Therefore, contact lenses (CLs) have emerged as an alternative drug-delivery system that prolongs drug retention in the cornea, improving its therapeutic performance. This study explores the in vitro ability of five commercially available hydrogel CLs to act as a delivery system for melatonin analogs and the in vivo secretagogue effect of melatonin analog-loaded CLs. We soaked CLs with melatonin or melatonin analog solutions (1 mM) for 12 h. Spectroscopic assays showed that IIK7-loaded CLs led to the inadequate delivery of this compound. Conventional hydrogel lenses loaded with agomelatine released more agomelatine than silicone ones (16–33% more). In contrast, the CLs of silicone materials are more effective as a delivery system of 5-MCA-NAT than CLs of conventional materials (24–29%). The adaptation of CLs loaded with agomelatine or 5-MCA-NAT in rabbits triggered a higher tear secretion than the corresponding eye drops (78% and 59% more, respectively). These data suggest that CLs preloaded with melatonin analogs could be an adequate strategy to combat aqueous tear deficient dry eye disease. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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7 pages, 518 KiB  
Article
The Impact of Noncontact Tonometry and Icare Rebound Tonometry on Tear Stability and Dry Eye Clinical Practice
by Murat Dogru, Cem Simsek, Takashi Kojima, Naohiko Aketa, Kazuo Tsubota and Jun Shimazaki
J. Clin. Med. 2022, 11(10), 2819; https://doi.org/10.3390/jcm11102819 - 17 May 2022
Cited by 1 | Viewed by 1394
Abstract
The purpose of this study was to investigate the possible effects of the noncontact air puff tonometry (NCT) and Icare rebound tonometry (ICT) on the tear film stability by using the tear stability analysis system (TSAS) and dry eye parameters. Fifteen eyes from [...] Read more.
The purpose of this study was to investigate the possible effects of the noncontact air puff tonometry (NCT) and Icare rebound tonometry (ICT) on the tear film stability by using the tear stability analysis system (TSAS) and dry eye parameters. Fifteen eyes from fifteen normal healthy subjects were investigated in this study. All subjects underwent TSAS surface regularity index (SRI) examinations, TBUT, and IOP measurements. The mean IOP results measured with NCT were 13.3 ± 1.86 mm Hg, and the mean IOP results measured with ICT were 15.88 ± 3.09 mm Hg (p > 0.05). The mean values of baseline, 5 min, and 10 min of the NCT-SRI and ICR-SRI were tested. There were statistically significant differences between NCT-Baseline SRI, NCT-5 min SRI, and NCT-10 min SRI values (p < 0.05). SRI values significantly increased after NCT. The mean values of the baseline, 5 min, and 10 min of the ICT-SRI were also assessed. There were no statistically significant differences between ICT-Baseline SRI, ICT-5 min SRI, and ICT-10 min SRI values (p > 0.05). The mean TBUT values exhibited a significant decrease at 1 min, 5 min, and 10 min compared with baseline values for the NCT and ICT (p < 0.01). NCT-TBUT and ICT-TBUT values were also compared with each other in the same time period. There were no statistically significant differences between NCT-Baseline and ICT-Baseline TBUT values (p > 0.05). In conclusion, intraocular pressure measurements in routine ophthalmology clinical practices by either NCT or ICT cause deterioration in the tear film stability which might affect tear stability testing when performed soon after IOP measurements. It is best to wait at least for 20–30 min after the IOP measurement before evaluating the tear film and the corneal surface or perform tonometry after the tear film-ocular surface evaluation tests. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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15 pages, 5904 KiB  
Article
Dermatochalasis Aggravates Meibomian Gland Dysfunction Related Dry Eyes
by Wan-Lin Wu and Shu-Wen Chang
J. Clin. Med. 2022, 11(9), 2379; https://doi.org/10.3390/jcm11092379 - 23 Apr 2022
Cited by 3 | Viewed by 2781
Abstract
This study aimed to investigate the relationships between subjective symptoms, objective signs, and dermatochalasis severity in dry-eye patients and the effects of lid hygiene on dry-eye parameters. We retrospectively enrolled 2328 patients who underwent dry-eye examinations and classified them into four groups by [...] Read more.
This study aimed to investigate the relationships between subjective symptoms, objective signs, and dermatochalasis severity in dry-eye patients and the effects of lid hygiene on dry-eye parameters. We retrospectively enrolled 2328 patients who underwent dry-eye examinations and classified them into four groups by dermatochalasis severity. The SPEED and OSDI questionnaires were used to evaluate subjective symptoms. LipiView® II interferometry was used to measure lipid-layer thickness (LLT) and blink/incomplete blink rates and perform meibography. A slit-lamp–aided standardized evaluator measured meibomian gland expressibility (MGE). A meiboscale was used to grade meibomian gland dropout. Fluorescein tear-film break-up time (FTBUT) and superficial punctate keratitis (SPK) were recorded. The Schirmer test II with anesthetics was used to evaluate aqueous tear secretion. The effects of lid hygiene were evaluated in 644 patients who underwent second comprehensive examinations. The median age of patients was 55.3 [46.0–66.0] years (76.0% female). Patients with more severe dermatochalasis were less symptomatic and had less MGE, higher meiboscale grades and average LLT. Dermatochalasis severity was significantly associated with MGE and meiboscale grade in the upper lid. There were no significant differences in the Schirmer test, FTBUT, and SPK among the severity groups. Females were older and had higher LLT and less severe dermatochalasis. Lid hygiene significantly decreased subjective symptoms, LLT, and Schirmer results, increased FTBUT, but did not change MGE or meiboscale grades. Dermatochalasis severity participated in the pathophysiology of dry eyes. Lid hygiene significantly improved subjective symptoms and reduced LLT, more significantly in patients with less severe dermatochalasis. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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12 pages, 4818 KiB  
Article
Comparison of Trehalose/Hyaluronic Acid (HA) vs. 0.001% Hydrocortisone/HA Eyedrops on Signs and Inflammatory Markers in a Desiccating Model of Dry Eye Disease (DED)
by Gloria Astolfi, Luca Lorenzini, Francesca Gobbo, Giuseppe Sarli and Piera Versura
J. Clin. Med. 2022, 11(6), 1518; https://doi.org/10.3390/jcm11061518 - 10 Mar 2022
Cited by 4 | Viewed by 2592
Abstract
Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo®, T/HA) with a tear substitute containing [...] Read more.
Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo®, T/HA) with a tear substitute containing 0.001% hydrocortisone (I) and 0.2% HA (Idroflog®, I/HA), with respect to changes on signs and inflammatory markers in a mouse DED model. Methods: Thirty 12-week-old C57BL/6 mice were exposed in a controlled-environment chamber as a desiccating stress model of DED for 35 days. At day 14 (T1), administration of 5 µL T or I in the right eye (RE) or NaCl 0.9% in the left eye (LE) started, twice a day. Animals were sacrificed after 7 (T2), 14 (T3), 21 (T4, endpoint) days from the beginning of treatment. Corneal fluorescein staining ratio (Image J), histological and histochemical assessment of ocular surface tissues (goblet cell GC density and characterization —PAS, Alcian blue pH 2.5, pH 1.0, and MUC4 expression—in the superior and inferior conjunctiva), and levels of inflammatory markers HLA-DR, IL-1β and TNF-α in cornea and conjunctiva were measured. Results: No animal fully recovered from DED signs at the endpoint. Difference between arms was observed at T3 and T4, with T treated eyes showing a higher corneal damage reduction, PAS-positive GC recovery, lower inflammatory marker expression as compared to the I treated ones. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 1057 KiB  
Article
Adherence to Eye Drops Usage in Dry Eye Patients and Reasons for Non-Compliance: A Web-Based Survey
by Miki Uchino, Norihiko Yokoi, Jun Shimazaki, Yuichi Hori, Kazuo Tsubota and on behalf of the Japan Dry Eye Society
J. Clin. Med. 2022, 11(2), 367; https://doi.org/10.3390/jcm11020367 - 12 Jan 2022
Cited by 22 | Viewed by 4514
Abstract
This study aimed to investigate the actual use of eye drops for dry eye disease (DED), the reasons for instillation behavior, and the relationship between instillation behavior and subjective symptoms. This web-based cross-sectional study collected data on instillation behavior, medication instruction, reasons for [...] Read more.
This study aimed to investigate the actual use of eye drops for dry eye disease (DED), the reasons for instillation behavior, and the relationship between instillation behavior and subjective symptoms. This web-based cross-sectional study collected data on instillation behavior, medication instruction, reasons for instillation behavior, and subjective symptoms. In total, 2645 participants were enrolled. The proportion of participants who instilled at the frequency specified in the package insert (the specified frequency) was 10.2%. The most common reason for not instilling at the prescribed frequency was as-needed instillation to alleviate subjective symptoms, and 61.3% of participants instilled when feeling symptoms. The improvement in the subjective symptoms score was significantly greater in the group that regularly instilled at the specified frequency than the other group (p = 0.0027), and patients in the other group were younger and had a higher rate of contact lens use and over-the-counter eye drops use. In conclusion, most participants did not instill the DED eye drops at the specified frequency to alleviate symptoms. In order to obtain the appropriate effect of eye drops, ophthalmologists need to impress upon patients the importance of regular instillation at the frequency specified in the package insert, while taking into account patient characteristics. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 1749 KiB  
Article
Analysis of the Association between Galectin-3 Concentration in Tears and the Severity of Dry Eye Disease: A Case-Control Study
by Miki Hata-Mizuno, Yuichi Uchino, Miki Uchino, Shigeto Shimmura, Yoko Ogawa, Kazuo Tsubota and Kazuno Negishi
J. Clin. Med. 2022, 11(1), 66; https://doi.org/10.3390/jcm11010066 - 23 Dec 2021
Cited by 1 | Viewed by 2305
Abstract
This study aimed to investigate the relationship between the severity of dry eye disease (DED) and galectin-3 concentration (gal-3) and its cleavage (gal-3C) in tear fluid. Twenty-eight DED patients and 14 controls were recruited at Keio University Hospital. The lissamine green conjunctival staining [...] Read more.
This study aimed to investigate the relationship between the severity of dry eye disease (DED) and galectin-3 concentration (gal-3) and its cleavage (gal-3C) in tear fluid. Twenty-eight DED patients and 14 controls were recruited at Keio University Hospital. The lissamine green conjunctival staining (LG) score, fluorescein corneal staining (FL) score, tear film break-up time (TBUT), Schirmer’s test, and ocular symptoms questionnaire score (dry eye questionnaire score, DEQS) were evaluated. Furthermore, the correlation between these parameters and the concentrations of gal-3 in tears (ng/µg) and the detection rate of gal-3C (%) were analyzed. Gal-3 concentration in tears was positively correlated with the LG score (R = 0.60, p < 0.01), FL score (R = 0.49, p < 0.01), and DEQS (R = 0.45, p < 0.01), and negatively correlated with the TBUT score (R = −0.40, p < 0.01) and Schirmer’s I value (R = −0.36, p < 0.01). The detection rate of gal-3C in tears was significantly associated with the severity of DED, especially with the LG (p < 0.01) and FL (p < 0.01) scores. Therefore, the concentration of gal-3 and the detection rate of gal-3C in tears had a significant relationship with the severity of ocular surface barrier disruption. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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9 pages, 1281 KiB  
Article
Hyaluronic Acid/Trehalose Ophthalmic Solution in Reducing Post-Cataract Surgery Dry Eye Signs and Symptoms: A Prospective, Interventional, Randomized, Open-Label Study
by Rita Mencucci, Eleonora Favuzza, Giulia Decandia, Michela Cennamo and Fabrizio Giansanti
J. Clin. Med. 2021, 10(20), 4699; https://doi.org/10.3390/jcm10204699 - 13 Oct 2021
Cited by 12 | Viewed by 2600
Abstract
The purpose of this prospective study was to evaluate the efficacy of the perioperative use of a hyaluronic acid (HA) and trehalose ophthalmic solution (Thealoz® Duo) in reducing post-cataract surgery dry eye signs and symptoms in patients with mild/moderate dry eye disease [...] Read more.
The purpose of this prospective study was to evaluate the efficacy of the perioperative use of a hyaluronic acid (HA) and trehalose ophthalmic solution (Thealoz® Duo) in reducing post-cataract surgery dry eye signs and symptoms in patients with mild/moderate dry eye disease (DED). One hundred and twenty patients, scheduled for unilateral cataract surgery, were randomized into three groups: (1) group A: HA/trehalose three times/day in the preoperative week and for 5 postoperative weeks; (2) group B: HA/trehalose for only 5 postoperative weeks; (3) group C: no artificial tears. In groups A and B, OSDI (Ocular Surface Disease Index) questionnaire scores were significantly lower than group C at all the postoperative visits; in group A they were significantly lower than group B on the day of surgery, with similar results in the first and fifth weeks after surgery. In groups A and B, break-up time (BUT) was significantly higher than group C during the postoperative period (p ≤ 0.001). In comparison to the preoperative values, BUT in group A remained stable 7 days after surgery; however, in groups B and C, it significantly decreased. In conclusion, the HA/trehalose ophthalmic solution effectively reduced post-cataract surgery DED signs and symptoms in patients with mild/moderate DED, particularly if also administered in the preoperative period. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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11 pages, 675 KiB  
Article
Characterization and Prediction of the Clinical Outcome of Intense Pulsed Light-Based Treatment in Dry Eye Associated to Meibomian Gland Dysfunction
by María T. Iradier, María Ángeles del Buey, Cristina Peris-Martínez, Priscilla Cedano and David P. Piñero
J. Clin. Med. 2021, 10(16), 3573; https://doi.org/10.3390/jcm10163573 - 13 Aug 2021
Cited by 5 | Viewed by 2000
Abstract
This non-comparative prospective case series was conducted to characterize the clinical impact of intense pulsed light (IPL)-based treatment in dry eyes associated to Meibomian gland dysfunction (MGD), defining the predicting factors for a successful outcome with this therapy in a large case series. [...] Read more.
This non-comparative prospective case series was conducted to characterize the clinical impact of intense pulsed light (IPL)-based treatment in dry eyes associated to Meibomian gland dysfunction (MGD), defining the predicting factors for a successful outcome with this therapy in a large case series. A total of 390 eyes (195 patients, range: 23–93 years) received four sessions of Optima IPL system (Lumenis, Yokneam, Israel). Significant changes were observed in tear film osmolarity in both eyes (p < 0.001) and in meibum quality (p < 0.001), with more eyes showing clear or yellow secretions after therapy. Mean change in the ocular surface disease index (OSDI) was −8.61, ranging from −27.00 to 11.00. This change was significantly correlated with the baseline value of OSDI (r = −0.489, p < 0.001). The change in osmolarity correlated significantly with the baseline osmolarity in both eyes (right r = −0.636, left r = −0.620, p < 0.001). A linear predicting model of the change in OSDI with therapy was obtained: change OSDI = 10.99 − 0.35 × OSDI − 1.03 × NIBUTRE-LE (mean non-invasive break up time of right and left eye) − 2.03 × Meibum quality grade (p = 0.001; R2: 0.325). In conclusion, the improvement in symptomatology achieved with an IPL-based therapy can be predicted at baseline using a linear model considering the level of MGD and the magnitude of OSDI and NIBUT (non-invasive break-up time). Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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11 pages, 265 KiB  
Article
Categorization of Marketed Artificial Tear Formulations Based on Their Ingredients: A Rational Approach for Their Use
by Avani Kathuria, Kiumars Shamloo, Vishal Jhanji and Ajay Sharma
J. Clin. Med. 2021, 10(6), 1289; https://doi.org/10.3390/jcm10061289 - 21 Mar 2021
Cited by 31 | Viewed by 6788
Abstract
Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of [...] Read more.
Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and preservatives. The currently marketed artificial tears can be grouped into four categories based on their active ingredients. The artificial tears also contain biologically active chemicals listed as inactive ingredients, which have osmoprotectant, humectant, and tear film lipid layer or mucous layer mimicking properties. Most artificial tears contain vanishing type preservatives such as purite or sodium perborate and safer quaternary compound polyquaternium-1. The majority of these artificial tear formulations are also available as preservative-free single dose unit. The study provides a formulary of artificial tears based on active ingredients, biologically active excipients, and the preservative-free option. The formulary should assist healthcare providers in making a stepwise and rational selection of appropriate artificial tears for patients suffering from dry eye disease. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
10 pages, 2695 KiB  
Article
A New Modified Experimental Meibomian Gland Injury Model: Partial Loss of Gland Due to Orifice Cauterization and the Alleviating Potential of 22-Oxacalcitriol
by Kai Jin, Motoko Kawashima, Masataka Ito, Reiko Arita, Kokoro Sano and Kazuo Tsubota
J. Clin. Med. 2021, 10(1), 6; https://doi.org/10.3390/jcm10010006 - 22 Dec 2020
Cited by 4 | Viewed by 2062
Abstract
1α,-25-dihydroxy-22-oxacalcitriol (maxacalcitol) is a non-calcemic vitamin D3 analog clinically approved to treat psoriasis, and its role has been increasingly recognized in suppressing keratinocyte proliferation, mediating inflammation, and regulating the immune response. A large number of studies have suggested that vitamin D plays an [...] Read more.
1α,-25-dihydroxy-22-oxacalcitriol (maxacalcitol) is a non-calcemic vitamin D3 analog clinically approved to treat psoriasis, and its role has been increasingly recognized in suppressing keratinocyte proliferation, mediating inflammation, and regulating the immune response. A large number of studies have suggested that vitamin D plays an important role in maintaining ocular surface health. However, its topical effects on the Meibomian gland (MG) has been insufficiently investigated. Here, we introduce an experimental MG orifice injury model, where the partial glandular loss occurred after electrical cauterization on a limited number of MG orifices, and investigate the efficacy and safety of maxacalcitol ointment in treating this MG orifice injury model. We confirm the alleviation of MG atrophy and ductal dilation by maxacalcitol ointment application. The recovery of injured MG visualizing as the residual MG area is significantly better in the maxacalcitol group (p = 0.020) compared with the Vaseline® group, especially during the first two weeks. The cornea and other ocular tissues were not affected by maxacalcitol ointment application during our two-month observation period. Altogether, this work indicates that maxacalcitol has therapeutic potential in the amelioration of initial injury of MG orifices caused by electrocautery. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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10 pages, 1811 KiB  
Article
Effect of Autologous Serum Eyedrops on Ocular Surface Disease Caused by Preserved Glaucoma Eyedrops
by Ha-Rim So, Hae Young Lopilly Park, So-Hyang Chung, Hyun-Seung Kim and Yong-Soo Byun
J. Clin. Med. 2020, 9(12), 3904; https://doi.org/10.3390/jcm9123904 - 01 Dec 2020
Cited by 5 | Viewed by 1966
Abstract
Autologous serum eyedrops (ASE) are effective in treating various ocular surface diseases, including damages induced by long-term use of preserved glaucoma eyedrops. However, there has been no study on whether ASE is effective without stopping the causative eyedrops. This retrospective observational study included [...] Read more.
Autologous serum eyedrops (ASE) are effective in treating various ocular surface diseases, including damages induced by long-term use of preserved glaucoma eyedrops. However, there has been no study on whether ASE is effective without stopping the causative eyedrops. This retrospective observational study included 55 patients with ocular-surface diseases caused by long-term use of preserved glaucoma eyedrops: 18 patients who used ASEs for 2 months without discontinuing the use of glaucoma eyedrops (Group 1), 22 patients who used ASEs for 2 months, discontinuing the use of glaucoma eyedrops for the first month (Group 2) and 15 patients who used non-preservative artificial tears for 2 months, discontinuing the use of glaucoma eyedrops for the first month (Group 3). There were no intergroup differences in the baseline values of the Schirmer I test results, tear breakup time (TBUT), ocular surface staining (OSS) score, loss of the meibomian gland, meibum quality and ocular-surface disease index (OSDI). Group 1 showed significant differences in TBUT, OSS score and OSDI at 2 months when compared to the baseline values before treatment, while Group 2 showed significant differences in those values at both 1 and 2 months. There were no differences in any of the parameters at baseline, 1 month or 2 months in Group 3. Our result suggested that ASE is effective for treating ocular surface diseases caused by glaucoma eyedrops containing preservatives and its effects can be expected without interruption of glaucoma eyedrop treatment. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 1552 KiB  
Systematic Review
The Efficacy and Safety of Rebamipide Ophthalmic Suspension (OPC-12759) in Patients with Dry Eye Disease: A Systematic Review of Randomized Controlled Trials
by Antonio Ballesteros-Sánchez, María Carmen Sánchez-González, Concepción De-Hita-Cantalejo, Estanislao Gutiérrez-Sánchez, Carlos Rocha-de-Lossada and José-María Sánchez-González
J. Clin. Med. 2023, 12(22), 7155; https://doi.org/10.3390/jcm12227155 - 17 Nov 2023
Viewed by 863
Abstract
The aim of this paper is to evaluate the efficacy and safety of Rebamipide (REB) ophthalmic suspension in dry eye disease (DED). A systematic review that only included full-length randomized controlled studies (RCTs) reporting the effects of REB ophthalmic suspension in three databases, [...] Read more.
The aim of this paper is to evaluate the efficacy and safety of Rebamipide (REB) ophthalmic suspension in dry eye disease (DED). A systematic review that only included full-length randomized controlled studies (RCTs) reporting the effects of REB ophthalmic suspension in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. A total of seven studies were included in this systematic review. Although the overall risk of bias was low, most studies were sponsored by the manufacturer. REB ophthalmic suspension treatment achieved higher improvement than the control group in all reported variables. The mean differences between both groups were in favor of the REB group and were as follows: dry eye-related quality of life score (DEQS) −3.5 ± 2.9 points, tear film break-up time (TBUT) of 0.7 ± 0.6 s, Schirmer test (ST) without anesthesia of 0.3 ± 0.6 mm and total corneal fluorescein staining (tCFS) of −1.2 ± 0.7 points. Adverse events (AEs) were 5.2 ± 7.6% superior in the REB group, with an overall compliance > 95%. Therefore, REB ophthalmic suspension is a safe and effective treatment that could be recommended in patients with DED. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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13 pages, 2489 KiB  
Systematic Review
Efficacy of Omega-3 Intake in Managing Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Wei-Xiang Wang and Mei-Lan Ko
J. Clin. Med. 2023, 12(22), 7026; https://doi.org/10.3390/jcm12227026 - 10 Nov 2023
Viewed by 1283
Abstract
To explore the efficacy of omega-3 fatty acids (FAs) on patients suffering from dry eye disease (DED), a complex inflammatory condition, we reviewed data from PubMed, Embase, ClinicalTrials.gov, Web of Science, and Cochrane CENTRAL in the past 10 years (2013 to 2023). These [...] Read more.
To explore the efficacy of omega-3 fatty acids (FAs) on patients suffering from dry eye disease (DED), a complex inflammatory condition, we reviewed data from PubMed, Embase, ClinicalTrials.gov, Web of Science, and Cochrane CENTRAL in the past 10 years (2013 to 2023). These sources provided randomized clinical trials (RCTs) that examined the efficacy of omega-3 FAs on DED patients with accessible pre- and post-intervention data, excluding trials with overlapping participants, without omega-3 supplementation, or those lacking placebo control or quantitative assessments. Two independent reviewers extracted data related to dry eye symptom scores, tear break-up time (TBUT), Schirmer’s tests, osmolarity, and corneal fluorescein staining (CFS), and the results were analyzed by Comprehensive Meta-Analysis software version 4. We incorporated 19 related RCTs assessed by the Cochrane Risk of Bias tool, encompassing 4246 DED patients with various etiologies. Patients given omega-3 treatment demonstrated more significant improvements in dry eye symptoms (Hedges’ g = −1.047; p < 0.001), TBUT [standardized mean difference (SMD) = −0.939; p < 0.001], scores from the Schirmer test (SMD = −0.372; p < 0.001), CFS (SMD = −0.299; p = 0.037), and osmolarity (SMD = −0.721; p < 0.001) compared to those on a placebo regimen. In the meta-regression analysis of DED symptoms, the daily dose of omega-3 (coefficient = −0.0005, p = 0.002), duration of omega-3 intake (coefficient = −0.1399, p = 0.021), and percentage of eicosapentaenoic acid (EPA) (coefficient = −0.0154, p < 0.001) exhibited a significant positive correlation with a reduction in dry eye symptom scores. Apart from CFS, similar trends were noted in TBUT, Schirmer tests, and osmolarity scores. Based on the evidence, omega-3 FAs effectively reduce DED symptoms, especially in high doses, for a long duration, and with increased EPA levels. However, given the heterogeneity in study results and diverse patient characteristics, caution is needed in generalizing these findings. In conclusion, omega-3 FA supplementation is still recommended for DED management in clinical settings. Full article
(This article belongs to the Special Issue Advances in Dry Eye Disease Treatment)
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