Comparison of Two Types of Artificial Tears

Study Overview
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Brief Summary
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Hyaluronic acid (HA), a natural component of the tear film, is a well-established active ingredient in artificial tears and has been reported to improve corneal and conjunctival staining in patients with DED. Thealoz Duo (Laboratoires Thea, Clermont Ferrand, France) is a novel artificial tear preparation containing two active ingredients: trehalose, a naturally occurring disaccharide with anhydrobiotic functions in many organisms, and hyaluronate, a widely distributed anionic glycosaminoglycan polysaccharide with lubricative and water-retaining properties in biological systems. The purpose of the current study is to investigate the effect of the Hyabak and Thealoz Duo in treatment of DED.

Detailed Description
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The patients will be treated with Thealoz Duo (at least 3 times daily) in one eye and with Hyabak (at least 3 times daily) in the other eye, based on randomization table. Both Hyabak and Thealoz Duo are preservative free. The doctors who examine the patients will not get any information about the choice of artificial tears in each eye. Besides the artificial tears, if necessary, the patients will receive other treatments, for instance, steroids, cyclosporine etc., according to their dry eye severity.

Official Title
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Comparison of the Efficacy of Two Types of Artificial Tears in the Treatment of Dry Eye Disease

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: Thealoz Duo (combination of trehalose and hyaluronate) eye drop and Hyabak (hyaluronate) eye drop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dry Eye Severity Level (DESL) 1-3 Equivalent between-eye DESL Exclusion Criteria: Ocular infection and/or non-linked inflammation Corneal pathology (except KSP) Corneal refractive surgery or cataract surgery within 6 months prior to the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Thealoz Duo<br>Thealoz Duo, a combination of trehalose and hyaluronate, will be used on one of the selected eyes of a patient, at least 3 times daily | Drug: Thealoz Duo (combination of trehalose and hyaluronate) eye drop and Hyabak (hyaluronate) eye drop<br>* One of the eyes will be assigned to use Thealoz Duo while the other with Hyabak by using randomisation table<br>|
| Active Comparator: Hyabak<br>Hyabak, sodium hyaluronate, will be used on the other eye of the patient, at least 3 times daily | Drug: Thealoz Duo (combination of trehalose and hyaluronate) eye drop and Hyabak (hyaluronate) eye drop<br>* One of the eyes will be assigned to use Thealoz Duo while the other with Hyabak by using randomisation table<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective dry eye symptoms | McMonnies dry eye questionnaire | Baseline, | 
| Subjective dry eye symptoms | McMonnies dry eye questionnaire | 1 month after treatment is initiated | 
| Subjective dry eye symptoms | McMonnies dry eye questionnaire | 3 months after treatment is initiated | 
| Subjective dry eye symptoms | Ocular Surface Disease Index (OSDI) dry eye questionnaire | Baseline | 
| Subjective dry eye symptoms | Ocular Surface Disease Index (OSDI) dry eye questionnaire | 1 month after treatment is initiated | 
| Subjective dry eye symptoms | Ocular Surface Disease Index (OSDI) dry eye questionnaire | 3 months after treatment is initiated | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein tear film break up time | Unit: seconds | Baseline | 
| Fluorescein tear film break up time | Unit: seconds | 1 month after treatment is initiated | 
| Fluorescein tear film break up time | Unit: seconds | 3 months after treatment is initiated | 
| Schirmer test | Without anaesthesia, recorded as mm in length of wetting after 5min | Baseline | 
| Schirmer test | Without anaesthesia, recorded as mm in length of wetting after 5min | 1 month after treatment is initiated | 
| Schirmer test | Without anaesthesia, recorded as mm in length of wetting after 5min | 3 months after treatment is initiated | 
| Ocular surface staining | Fluorescein staining at the conjunctiva and cornea. Recorded using oxford scheme, range 0-15 | Baseline | 
| Ocular surface staining | Fluorescein staining at the conjunctiva and cornea. Recorded using oxford scheme, range 0-15 | 1 month after treatment is initiated | 
| Ocular surface staining | Fluorescein staining at the conjunctiva and cornea. Recorded using oxford scheme, range 0-15 | 3 months after treatment is initiated | 
| Tear film osmolarity | Unit: Osm/L | Baseline | 
| Tear film osmolarity | Unit: Osm/L | 1 month after treatment is initiated | 
| Tear film osmolarity | Unit: Osm/L | 3 month after treatment is initiated | 
| Meibum expressibility | Evaluated by application of light pressure using cotton tips on the central five MGs of the lower eyelid. Expression was graded according to the number of the MGs with meibum secretion under pressure: grade 0: 5 glands; grade 1: 3-4 glands; grade 2: 1-2 glands; grade 3: 0 gland | Baseline | 
| Meibum expressibility | Evaluated by application of light pressure using cotton tips on the central five MGs of the lower eyelid. Expression was graded according to the number of the MGs with meibum secretion under pressure: grade 0: 5 glands; grade 1: 3-4 glands; grade 2: 1-2 glands; grade 3: 0 gland | 1 month after treatment is initiated | 
| Meibomian gland functionality | Meibum expressibility and quality | 3 months after treatment is initiated | 
| Meibum quality | The quality of the meibum that was secreted from each gland was graded as following: 0, clear; 1, cloudy; 2, cloudy with particles; and 3, toothpaste like. The sum of the score of the central 8 glands in the lower eyelid will be recorded | Baseline | 
| Meibum quality | The quality of the meibum that was secreted from each gland was graded as following: 0, clear; 1, cloudy; 2, cloudy with particles; and 3, toothpaste like. The sum of the score of the central 8 glands in the lower eyelid will be recorded | 1 month after treatment is initiated | 
| Meibum quality | The quality of the meibum that was secreted from each gland was graded as following: 0, clear; 1, cloudy; 2, cloudy with particles; and 3, toothpaste like. The sum of the score of the central 8 glands in the lower eyelid will be recorded | 3 months after treatment is initiated | 
| Patient´s subjective evaluation of preference | Patients will be asked about which artificial tear they prefer | 1 month after the treatment is initiated | 
| Patient´s subjective evaluation of preference | Patients will be asked about which artificial tear they prefer | 3 months after the treatment is initiated | 
| Luminex | A multiplex Luminex® bead-based assay will be used to analyze cytokines from the tear samples. The cytokines to be analysed include 27 different cytokines, including interleukin 1b (IL-1b), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-1 receptor antagonist (IL-1ra), eotaxin, basic fibroblast growth factor (bFGF/FGF2), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α/CCL3), MIP-1b, platelet-derived growth factor bb (PDGF-BB), regulated-on-activation normal T cell expressed and secreted (Rantes), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). | Baseline | 
| Luminex | A multiplex Luminex® bead-based assay will be used to analyze cytokines from the tear samples. The cytokines to be analysed include 27 different cytokines, including interleukin 1b (IL-1b), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-1 receptor antagonist (IL-1ra), eotaxin, basic fibroblast growth factor (bFGF/FGF2), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α/CCL3), MIP-1b, platelet-derived growth factor bb (PDGF-BB), regulated-on-activation normal T cell expressed and secreted (Rantes), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). | 1 month after treatment is initiated | 
| Luminex | A multiplex Luminex® bead-based assay will be used to analyze cytokines from the tear samples. The cytokines to be analysed include 27 different cytokines, including interleukin 1b (IL-1b), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-1 receptor antagonist (IL-1ra), eotaxin, basic fibroblast growth factor (bFGF/FGF2), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α/CCL3), MIP-1b, platelet-derived growth factor bb (PDGF-BB), regulated-on-activation normal T cell expressed and secreted (Rantes), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). | 3 months after treatment is initiated |