Effectiveness and Safety of Intense Pulsed Light in Patients With Meibomian Gland Dysfunction

Study Overview
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Brief Summary
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Meibomian gland dysfunction (MGD) is one of the most common causes of dry eye diseases. Over the past decade, several treatment options in MGD have been extensively studied including warm compression, lid hygiene, ocular lubricants, forceful expression, LipiFlow thermal pulsation system, intraductal probing, debridement scaling and intense pulsed light (IPL). IPL is a broad spectrum, non-coherent and polychromatic light source with a wavelength spectrum of 500-1200 nm. It can be filtered to allow only a range of wavelengths to be emitted. Different wavelength makes different depth of tissue to absorb a specific light energy. Intense pulsed light (IPL) has been widely used in dermatology as a therapeutic tool for removal of hypertrichosis, benign cavernous hemangioma, benign venous malformations, telangiectasia, port-wine stain and pigmented lesions. Concurrent ocular surface improvements have been observed in patients undergone IPL treatment. Very few prospective clinical trials showed that subjective dry eye symptoms decreased and some of the dry eye signs also improved. Nonetheless, there is still inconsistency in the efficacy of IPL among these studies. Biomarkers, specifically cytokines, in dry eye diseases have been studied to some extent. Moreover, the change in ocular surface inflammatory cytokines in patients with MGD after IPL treatment is unclear. The investigators proposed a prospective randomized double-masked sham-controlled clinical trial to investigate the efficacy and safety of intense pulse light in MGD patients.

Official Title
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Effectiveness and Safety of Intense Pulsed Light in Patients With Meibomian Gland Dysfunction

Conditions
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Meibomian Gland Dysfunction (Disorder), Dry Eye Syndromes

Intervention / Treatment
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* Device: Intense Pulsed Light
* Combination Product: Standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read, understand and sign an informed consent form 18-80 years of age Fitzpatrick skin type 1-5 Able and willing to comply with the treatment /follow-up schedule and requirements Presence of meibomian gland on each lower eyelid's meibography Current diagnosis of stage1-4 of MGD in both eyes, according to the International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction Exclusion Criteria: Contact lens wearer within the past 1 month and throughout the study Recent ocular surgery or eyelid surgery within the past 6 months Neuro-paralysis in the planned treatment area within the past 6 months Current use of punctual plugs Pre-cancerous lesions, skin cancer or pigmented lesions in the planned treatment area Uncontrolled infections or uncontrolled immunosuppressive diseases Subjects who have undergone refractive surgery within the past 6 months Diseases in the planned treatment area that could be stimulated by light at 560 nm to 1200 nm (e.g.,Herpes simplex 1 and 2, Systemic Lupus Erythematosus, porphyria) Use of photosensitive medications and/or herbs that may cause sensitivity to 560-1200 nm light exposure, such as isotretinoin, tetracycline, or St. John's Wort Pregnancy and lactation Radiation therapy to the head or neck within the past year, or planned radiation therapy throughout study period Treatment with chemotherapeutic agent within the past 8 weeks, or planned chemotherapy throughout study period Any condition revealed during the eligibility screening process whereby the physician deems the subject inappropriate for this study Declared legally blind in one eye IPL treatment within the past 12 months Lipiflow treatment, or any equivalent treatments, within the past 12 months Any anti-glaucomatous eye drop uses within the past 3 months and throughout the study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPL group<br>IPL 9-13 J/cm2 according to Fitzpatrick's skin type on day 0, 15, 45 | Device: Intense Pulsed Light<br>* E> Eye (E-SWIN, Paris, France) IPL machine<br>Combination Product: Standard treatment<br>* warm compression, lid scrub and non-preservative ocular lubricants<br>|
| Sham Comparator: sham-IPL group<br>IPL 0 J/cm2 according to Fitzpatrick's skin type on day 0, 15, 45 | Combination Product: Standard treatment<br>* warm compression, lid scrub and non-preservative ocular lubricants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fluorescein tear break-up time at month 6 using fluorescein technique | time elapsed from the last complete eyelid blink until appearance of the first dry spot on the cornea | day 0, 15, 45, month 3, month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dry eye symptoms using Ocular Surface Disease Index (OSDI), a questionnaire, at month 6 | a 12-item questionnaire designed to provide a rapid assessment of the symptoms of ocular irritation consistent with dry eye disease and their impact on vision-related functioning. | day 0, 15, 45, month 3, month 6 | 
| Change in lipid layer thickness at month 6 using LipiView interferometer (TearScience inc., Morrisville,NC) | quantitative values of the tear-film lipid layer depth or thickness by imaging the surface contour of the tear film, lipid layer thickness measurement | day 0, 15, 45, month 3, month 6 | 
| Change in Meibomian gland's anatomy by Meiboscore using Meibography at month 6 using Keratograph 5M (OCULUS, Wetzlar, Germany) | directly visualising the morphology of meibomian glands in vivo | day 0, 15, 45, month 3, month 6 | 
| Change in ocular surface staining at month 6 using fluorescein staining technique | fluorescein dye which is a mildly invasive stain that marks the tear film and defects in the corneal and conjunctival epithelium. The investigators use National Eye Institute (NEI) grading for ocular surface staining score in this study | day 0, 15, 45, month 3, month 6 | 
| Change in Meibomian gland expressibility at month 6 after applying the force onto the eyelids using meibomian gland evaluator | number of glands expressible after applying force onto the eyelids | day 0, 15, 45, month 3, month 6 | 
| Change in Meibum quality at month 6 after applying the force onto the eyelids using meibomian gland evaluator | quality of the meibum content after applying the force onto the eyelids | day 0, 15, 45, month 3, month 6 | 
| Change in tear osmolarity at month 6 using TearLab Osmolarity System (San Diego, CA) | concentration of the tear : The investigators use TearLab Osmolarity System (San Diego, CA) | day 0, 45, month 3, month 6 | 
| Change in tear production test (Schirmer's test) at month 3 using calibrated strips of a non-toxic filter paper | is used determine whether the lacrimal glands produce enough tears to keep the eyes adequately moist | day 0, month 3 | 
| Change in tear cytokines Interleukins-1 receptor antagonist (IL-1Ra) at month 3 using Bio-Plex® 200 system (Bio-Rad, Hercules, CA) | one of the tear inflammatory cytokines | day 0, month 3 | 
| Change in tear cytokines Interleukins-6 at month 3 using Bio-Plex® 200 system (Bio-Rad, Hercules, CA) | one of the tear inflammatory cytokines | day 0, month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intense pulsed light, Meibomian gland dysfunction, Dry eye, cytokines