Temperature on Evaporative Dry Eye

Study Overview
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Brief Summary
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Ocular surface temperature of a normal person is around 34.6 degree centigrade. After instilling the eye drop, depending on the temperature of the eye drop and the ocular surface, the ocular surface temperature will temporally increase or decrease sightly. Warm feeling will make blood vessels dilated and more blood will pass through to bring more blood flow out of our body to the heated area of the body and makes cells more permeable. Therefore, heating the ocular surface with heated eye mask after instilling artificial tears has the possibility to improve drug permeability on the ocular surface.

Detailed Description
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Evaporative dry eye (EDE) is common and can lead to ocular pain, decreased visual quality, and reduced quality of life. 3% diquafosol (DQS) ophthalmic solution and heated eye mask (HEM) have been found to be beneficial in reducing signs and symptoms of dry eye. Warm compress therapy temperature of 40 °C to 45 °C have been typically advocated to melt the meibium causing obstruction at the orifices of the meibomian gland, eventually allowing increased lipid layer of the tear film. While in impact of heat on the ocular surface (OS) has not been extensively studied. Controlled and precise application of heat has the ability to create a cascade of events in the skin and thus aids in facilitating a faster movement of molecules into and across the skin. Possible mechanisms of enhancing drug permeation include on the ocular surface could be: (mechanisms may operate individually or concurrently): increase in drug diffusivity in the vehicle and/or in the ocular surface increase in partitioning and diffusion alteration in the lipid structure increased local blood flow Therefore, the purpose of this RCT is to assess the impact of instilling 3% DQS ophthalmic solution follow by HEM raising the OS temperature by 40 degrees centigrade for 10 minutes.

Official Title
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Safety and Efficacy of Heated Artificial Tears Under Practical Conditions

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Diquafosol tetrasodium
* Device: Heated eye mask


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years The presence of at most one symptom including burning, foreign body sensation, itching or eye fatigue for 3 months OSDI score ≥ 13 and TBUT <5 s or NIBUT < 10s Able and willing to comply with the treatment/follow-up schedule Exclusion Criteria: A recent history (past 30 days) of topical ophthalmic medication use, including antibiotics, steroids, non-steroidal anti-inflammatory drugs, or required the chronic use of topical ophthalmic medications Eyelids or intraocular tumors that should not put pressure Active allergy or infection or inflammatory disease that may have prevented the subjects from completing the study at the ocular surface Any structural change in lacrimal passage Glaucoma Diabetes or other systemic, dermatologic, or neurologic diseases that affect the health of ocular surface Use of any systemic anti-inflammatory drugs or medication that may interfere with tear production, such as antianxiety, antidepressive, and antihistamine medications within 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DQS+HEM<br>Participants in the DQS+ group used DQS 1 drop 3 times/per day with heated eye mask for 2 weeks | Drug: Diquafosol tetrasodium<br>* 3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in dry eye signs and symptoms<br>* Other names: Diquas;Device: Heated eye mask<br>* Heated eye mask will be used to assess its usefulness in dry eye signs and symptoms<br>|
| Active Comparator: DQS<br>Participants in the DQS group used DQS 1 drop 3 times/per day for 2 weeks | Drug: Diquafosol tetrasodium<br>* 3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in dry eye signs and symptoms<br>* Other names: Diquas;|
| Active Comparator: HEM<br>Participants in the HEM group used heated eye mask 3 times/per day for 2 weeks | Device: Heated eye mask<br>* Heated eye mask will be used to assess its usefulness in dry eye signs and symptoms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-invasive tear break-up time (NIBUT) | Non-invasive initial tear film breaking time will be assessed using the Keratograph 5M (Oculus, Germany) topographer. Three sequentially readings will be captured, and the median value will be included in the final analysis. The median value will be recorded. Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 
| Ocular Surface Disease Index (OSDI) | OSDI, which is a questionnaire consisting of 12 questions for evaluating the effects of dry eye syndrome on vision, ocular symptoms and any condition associated with DED. The patient will answer each question on a scale ranging from 0 to 4, with 0 indicating 'none of the time' and 4 indicating 'all of the time'. If a certain question is deemed irrelevant, it will be marked as 'not applicable (N/A)' and excluded from the analysis. The OSDI total score is calculated according to the following formula. The scale ranges from 0 to 100, with higher scores representing more severe cases of dry eye syndrome. Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined | Day-0 (baseline), day-7, and day-14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein and lissamine conjunctival and cornea staining (CFS) | Fluorescein and lissamine staining of the ocular surface will be divided into three zones comprising nasal conjunctival, corneal, and temporal conjunctival areas. The staining score ranged from 0 to 3 for each zone, yielding a total score of 0-9 for the ocular surface. Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 
| Meibomian gland function and secretion quality | Meibum quality will be assessed under a slit-lamp: Five meibomian gland in the middle parts of the eyelid will be assessed using a scale of 0 to 3 for each gland (0 represented clear meibum; 1 represented cloudy meibum; 2 represented cloudy and granular meibum; and 3 represented thick, toothpaste like consistency meibum) Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 
| Tear Film Lipid Layer Score (TFLL) | Tear Film Lipid Layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan). The results will be graded as follows: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; grade 5, corneal surface partially exposed. Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 
| Tear meniscus height (TMH) | Non-invasive first tear film breakup time using the Keratograph 5M (Oculus, Germany) topographer will be measured three times consecutively and the median value was recorded. Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 
| Conjunctival hyperemia (RS score) | Conjunctival hyperemia (RS score) will be assessed by Keratograph image (Oculus, Germany) of 1156*873 pixels, redness score (RS) (accurate to 0.1 U) was displayed on the computer screen that ranged from 0.0 (normal) to 4.0 (severe). Changes at day-14 and day-28 will be compare with baseline measurements. Comparison between groups at baseline, day-14 and day-28 will also be examined. | Day-0 (baseline), day-7, and day-14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dry eye, heated eye mask, diquafosol, tear breakup time, ocular surface disease index