Feasibility of IPL Combined With RF for Treatment of DED Due to MGD

Study Overview
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Brief Summary
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The purpose of this single-arm pilot study is to evaluate the feasibility and safety of combination therapy of intense pulsed light (IPL) and (Radiofrequency) RF for treatment of Dry eye disease (DED) due to Meibomian gland dysfunction (MGD).

Detailed Description
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In the past several years, a large number of studies have demonstrated that several sessions of IPL followed by MGX lead to a long-term reduction in signs and symptoms of DED due to MGD, however benefits for the patient are expected only after 2 or 3 sessions. On the other hand, several researchers reported that application of RF around the eyelids provide immediate relief of DED symptoms (unpublished observations: Dr. Chantel Garcia). The efficacy of RF for reduction of DED signs and symptoms was also demonstrated in two clinical studies and one animal model of obstructive MGD. Despite the small number of studies with RF, these preliminary results suggest that the combination of IPL, MGX and RF could provide immediate symptomatic relief together with long-term improvement of signs and symptoms of DED. In addition, combination therapy might be useful to increase the efficacy of monotherapy RF or monotherapy IPL. The purpose of this single-arm pilot study is to evaluate the feasibility and safety of combination therapy of IPL and RF for treatment of DED due to MGD. As far as we know this is the first study of its kind. Results of this current study will be useful to choose the most effective outcome measures, to estimate the risk to benefit ratio, and to anticipate the effect size. In the future, such information will be essential for evaluating the merits of this approach, by designing a powered and randomized controlled study. .

Official Title
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Feasibility of IPL Combined With RF for Treatment of DED Due to MGD

Conditions
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Dry Eye Disease, Meibomian Gland Dysfunction

Intervention / Treatment
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* Device: IPL_RF_MGX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able to read, understand and sign an IC form 22 or older Self-assessed symptoms are consistent with moderate to severe dry eye (OSDI score ≥ 23) Signs of MGD, as detected in biomicroscopy Modified Meibomian Gland Score (mMGS) > 12 in the lower eyelid of at least one eye Fitzpatrick skin type I-IV Subject is willing to comply with all study procedures Exclusion Criteria: Fitzpatrick skin type V or VI Pacemaker Any metal implants above the neck, excluding dental implants Dry Eye due to Sjogren LASIK/SMILE surgery, within 1 year prior to screening RK surgery Other ocular surgery or eyelid surgery, within 3 months prior to screening Recent ocular trauma, within 3 months prior to screening Pre-cancerous lesions or skin cancer in the planned treatment area Severe active allergies, or other severe uncontrolled eye disorders affecting the ocular surface Uncontrolled infections or uncontrolled immunosuppressive diseases Legally blind in either eye worse than 20/200 Ocular surface abnormality that may compromise corneal integrity in either eye (e.g., prior chemical burn, Epithelial Basement Membrane Dystrophy (EBMD) Eyelid abnormalities that affect lid function in either eye, including: entropion, ectropion, tumor, blepharospasm, Grading staining in the lower third secondary to lagophthalmos, severe trichiasis, and severe ptosis Within 3 months prior to screening, use of photosensitive medication and/or herbs that may cause sensitivity to 560-1200 nm light exposure, including: Isotretinoin, Tetracycline, Doxycycline, and St. John's Wort Active sun burn in the treatment area Moderate to severely compromised corneal health as assessed by corneal fluorescein staining Anterior chamber inflammation Corneal edema 4 weeks wash out of all prescription eye drops, excluding artificial lubricants No more than 75% loss of meibomian glands, as evaluated with meibography, in either lower eyelid Any non-prescription product for dry eye, within 1 month from the study, excluding artificial lubricants Any condition revealed whereby the investigator deems the subject inappropriate for this study

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study arm<br>Subjects will receive 4 treatments at 2-weeks intervals. Each treatment will consist of IPL administered on the malar region, followed by RF administered around the eye, followed by Meibomian gland expression (MGX). Follow-up will be conducted at 4 weeks after the 4th treatment session. | Device: IPL_RF_MGX<br>* intense pulsed light followed by Radiofrequency followed by meibomian gland expression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified meibomian gland score (mMGS) | 15 meibomian glands along the lower lid (5 nasal + 5 central + 5 temporal) will be gently expressed with the dedicated expression forceps. Each gland will be scored 0 to 3, as follows: 0 = clear liquid meibum; 1 = cloudy liquid meibum; 2 = inspissated meibum; 3 = blocked). mMGS will be evaluated as the sum of scores for these 15 glands. | 4 weeks after the 4th treatment session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OSDI | Ocular Surface Disease Index questionnaire | 4 weeks after the 4th treatment session | 
| Eyelid appearance | Eyelid appearance will be assessed with biomicroscopy at the slit lamp. Five features of the eyelids will be scored: lid margin vascularity, eyelid thickness, loss of eyelashes, conjunctival injection, and plugging of meibomian gland orifices. Each feature will be scored using a 4 point grading system: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. | 4 weeks after the 4th treatment session | 
| Number of expressible glands | Glands along the upper and lower lids will be squeezed with a dedicated expression forceps. The number of glands expressing any meibum (clear liquid, cloudy liquid, or inspissated) will be counted, per each eyelid separately. | 4 weeks after the 4th treatment session | 
| NIBUT | The non-invasive breakup time (NIBUT) will be measured with the tear film analysis feature of the Antares system (CSO). The subject will be asked to maintain his/her eye open, without blinking, in front of a device that will project concentric Placido disks will be projected onto the ocular surface. Mire reflections of these placido disks will be monitored. The first occurrence of image distortion will | 4 weeks after the 4th treatment session | 
| Meibography | The study investigator will invert the eyelids of the subject, to expose the meibomian glands. After viewing the inverted eyelids with infra-red light illumination using the Antares system (CSO), an infra-red image of the meibomian glands will be captured cand saved. The Antares software will be use to calculate the area of meibomian gland loss | 4 weeks after the 4th treatment session |