Efficacy and Safety of Thermic Devices in the Treatment of Meibomian Gland Dysfunction

Study Overview
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Brief Summary
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Dry eye syndrome is a common eye disease that affects 1 to 2 out of 10 persons around the planet. One common cause of this disease is the meibomian gland dysfunction. Meibomian glands are very small glands located at the rim of the eyelids that produce an oily substance that prevents the evaporation of tears. When these glands are compromised, the tear film evaporates quickly and the eyes dry up. This disease presents as eye irritation, foreign body sensation, inflammation, etc. The treatment of choice for MGD is eyelid massage and warm compresses 2 times a day. However, these treatments not always work perfectly, and as a result, patients find it hard to follow doctor's orders. Another kind of treatment is thermal therapy. There are several devices that are designed to apply heat on the eyelids, such as Lipiflow, MiBo Thermoflo, and Blephasteam. In this study, we want to find out whether thermal therapy with MiBo Thermoflo works better than warm compresses and eyelid massage use in the treatment of dry eye caused by MGD. To do this, we will select several patients and will assign them randomly to either the group with thermal therapy with MiBo Thermoflo or to the group with warm compresses and eyelid massage. The Mibo group will receive 3 sessions of thermal therapy at 2 weeks interval and the control group warm compresses and eyelid massage 2 times per day. All subjects will have a follow up of 24 weeks and we will compare results for both groups at the end of the study.

Detailed Description
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Dry eye syndrome is considered one of the most important ophthalmologic diseases, affecting 10 to 20% of the general population. Of these, 3.7% to 70% of cases are due to meibomian gland dysfunction (MGD). MGD is a chronic diffuse disease characterized by terminal duct obstruction and/or qualitative/quantitative changes in gland secretion. This causes a disruption in the tear film, ocular irritation symptom, inflammation, and ocular surface symptoms. The gold standard for the treatment of meibomian dysfunction is the use of warm compresses and eyelid massage 2 times a day. These have variable results and consequently patient's adherence to treatment is low. An alternative treatment is the use of thermal therapy devices such as Lipiflow, MiBo Thermoflo, and Blephasteam. The objective of this study is to determine if the thermal device MiBo Thermoflo is more effective than warm compresses and eyelid massage in the treatment of dry eye secondary to MGD. Participants will be randomly assigned to one of two groups: the Mibo group will receive 3 sessions of thermal therapy at 2 weeks interval and the control group warm compresses and eyelid massage 2 times per day. All subjects will have follow up of 24 weeks and we will compare results for both groups at the end of the study. During the protocol patients in both groups will continue with their standard treatment for dry eye as needed.

Official Title
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Efficacy and Safety of Thermic Devices in the Treatment of Meibomian Gland Dysfunction

Conditions
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Meibomian Gland Dysfunction

Intervention / Treatment
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* Device: Mibo Thermoflo
* Other: Warm compresses and eyelid massage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with: Dry eye syndrome with meibomian gland dysfunction alone or in combination of other type of dry eye. Patients who were previously treated with eyelid massages and warm compresses without any improvement. Exclusion Criteria: Pregnant women. History of ocular surgery within three months prior to inclusion. History of trauma, infection or inflammation within three months prior to inclusion. Contact lens use in the last week before inclusion. Patients with active ocular allergic disease. Patient with microbial keratitis.

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
Interventional Model Description: All subjects will be ophthalmologically evaluated before treatment and at weeks 8, 16 and 24. Subjects will be randomly assigned into 2 study groups. Mibo group will have 3 sessions (basal, week 2, week 4) of thermal therapy with Mibo Thermoflo in both eyes. The control group will use warm compresses and eyelid massage 2 times per day in both eyes. At the week 16 control group will also have 3 sessions of Mibo therapy at 2 weeks interval.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mibo Thermoflo (thermal device)<br>3 sessions at 2 weeks interval (basal, week 2, week 4)of 11 minutes per eye of thermal therapy with Mibo Thermoflo. | Device: Mibo Thermoflo<br>* Thermal therapy with Mibo Thermoflo for 11 minutes per eye, during each session.<br>|
| Active Comparator: Warm compresses and eyelid massage<br>2 times per day, 11 minutes per eye. | Other: Warm compresses and eyelid massage<br>* Warm compresses plus eyelid massage 2 times per day 11 minutes per eye.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Meibomian gland expressibility | Changes in meibomian gland structure will be evaluated by meibomian gland expressibility. | Basal to 24 weeks | 
| Meibum quality | Changes in meibomian gland structure will be evaluated with the meibum quality in slit lamp graded as: clear, opaque, granular and toothpaste for meibum worst secretion. | Basal to 24 weeks | 
| Corneal and conjunctival staining with fluorescein dye | Ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye. | Basal to 24 weeks | 
| Corneal and conjunctival staining with lissamine green dye | Ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye. | Basal to 24 weeks | 
| Tear Break-up Time (TBUT) | Tear stability will be measured with Tear Break-up Time (TBUT). A result >10 seconds will be considered normal, a result <10 seconds will be considered pathological. | Basal to 24 weeks | 
| Schirmer test with and without anesthesia | Tear production will be measured by Schirmer test with and without anesthesia. A Schirmer test >10 mm will be considered normal, a result >5 mm pathological. The Schirmer test with anesthesia >15 mm is consider normal. | Basal to 24 weeks | 
| Symptom Assessment in Dry Eye questionnaire (SANDE) | Ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE) questionnaire. The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms. | Basal to 24 weeks | 
| Ocular Surface Disease Index (OSDI) | Ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients are asked to rate their responses on a 0 to 4 scale where 0 represents none of the time, 1 some of the time, 2 half of the time, 3 most of the time, and 4 all of the time. The total score is calculated using the following formula: ([sum of scores for all questions answered x 100] / [total number of questions answered x 4]). Lower scores represent a better outcome. | Basal to 24 weeks | 
| Dry Eye Questionnaire 5 (DEQ-5) | Ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level. | Basal to 24 weeks | 
| Tear osmolarity | Patients with dry eye have increased levels of tear osmolarity wich is one of tear inflammation biomarkers. Tear osmolarity will be performed with Tear Lab Osmolarity System, a result of 308 mOsm/L or higher indicates dry eye disease. | Basal to 24 weeks | 
| Change in tear of matrix metalloproteinase 9 (MMP-9) | MMP-9 is an inflammatory biomarker wich is elevated in the tears of patients with dry eye and an early diagnostic evaluation, it is realized in consulting room with the InflammaDry test (Rapid Pathogen Screening Inc.). The presence of 1 line is a negative result and two lines means positive result. | Basal to 24 weeks | 
| Non-Invasive Keratograph Break-up Time (NIKBUT) | NIKBUT will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. | Basal to 24 weeks | 
| Tear meniscus height | Tear meniscus height will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. | Basal to 24 weeks | 
| Conjuctival hyperemia | Conjuctival hypermeia will be graded with JENVIS Scale performed by Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. Conjuctival hyperemia will be . graded as: none, mild moderate or severe. | Basal to 24 weeks | 
| Lipid layer thickness | Lipid layer thickness will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. | Basal to 24 weeks | 
| Adverse events | Adverse events will be evaluated during the ophthalmic evaluation. | Basal to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short term changes with corneal and conjunctival staining with fluorescein dye | Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Short term changes with corneal and conjunctival staining with lissamine green dye | Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Short term changes in tear stability | Short term changes in tear stability will be measured with Tear Break-up Time (TBUT). A result >10 seconds will be considered normal, a result <10 seconds will be considered pathological. | These parameterd will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Short term changes in Symptom Assessment in Dry Eye questionnaire (SANDE) | Short term changes in ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE). The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms. A less rate prove changes in ocular surface symptoms and quality of life improvement. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Short term changes in Ocular Surface Disease Index (OSDI) | Short term changes in ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers.. A less rate prove changes in ocular surface symptoms and quality of life improvement. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Short term changes in Dry Eye Questionnaire 5 (DEQ-5) | Short term changes in ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level. A less rate prove changes in coular surface symptoms and quality of life improvement. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Eyelid skin temperature | Eyelid skin temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Corneal conjunctival temperature | Corneal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Bulbar conjunctival temperature | Bulbar conjunctival temperature will be measured with the thermographic infrrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends. | These parameters will be evaluated before sessions of termal therapy at week 2 and week 4 | 
| Tarsal conjunctival temperature | Tarsal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends. | These parameters will be evaluated before sessions of thermal therapy at week 2 and week 4. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meibomian gland dysfunction, Mibo, MGD, Dry eye disease, Thermic devices