Effectiveness and Safety of High Frequency Electrotherapy in Patients With Meibomian Gland Dysfunction

Study Overview
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Brief Summary
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This study is a prospective randomized double-masked sham-controlled clinical trial to determine the clinical improvement, safety and mechanism of action by evaluation inflammatory cytokine, and amount of bacteria and demodex, after high frequency electrotherapy or called quantum molecular resonance treatment in patients with meibomian gland dysfunction.

Detailed Description
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The Rexon-eye is quantum molecular resonance device which was published in previous study that could treat meibomian gland dysfunction. Participants in this study will have Rexon-eye treatment at baseline (after recording of baseline characteristics and giving and inform consent), day 7, day 14, day 21. The evaluation for most parameter except for safety parameter will be recorded at baseline, 1 month after last treatment, and 2 mont after last treatment. Safety parameter will be recorded in all 4 follow-ups. During study, all participant will instructed to use same artificial tears for four time a day.

Official Title
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Effectiveness and Safety of High Frequency Electrotherapy in Patients With Meibomian Gland Dysfunction : Randomized Controlled Trial

Conditions
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Meibomian Gland Dysfunction

Intervention / Treatment
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* Device: Rexon-eye


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read, understand and sign an informed consent form > 18years of age 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 stage 1-4 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 punctal 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 Patients who had ocular infection within 6 months Pregnancy and lactation Any condition revealed during the eligibility screening process whereby the physician deems the subject inappropriate for this study Declared legally blind in one eye Lipiflow treatment, or any equivalent treatments, within the past 12 months

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>This treatment is delivered by contact electrodes built in a mask, which is worn by the patient over closed eyes. The device setup is really easy and intuitive. | Device: Rexon-eye<br>* a technique in which low-intensity, high-frequency (a spectrum of frequencies ranging from 4 MHz to 64 MHz) electric currents are administered to a biological tissue through contact electrodes<br>* Other names: Quantum Molecular Resonance device;|
| Sham Comparator: Sham-intervention<br>The same device as treatment but the power of device will be set to ZERO power. | Device: Rexon-eye<br>* a technique in which low-intensity, high-frequency (a spectrum of frequencies ranging from 4 MHz to 64 MHz) electric currents are administered to a biological tissue through contact electrodes<br>* Other names: Quantum Molecular Resonance device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| non-invasive tear break-up time (NITBUT) | Change from baseline NITBUT at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| non-invasive tear break-up time (NITBUT) | Change from baseline NITBUT at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Index Score scored (OSDI score) | Change from baseline OSDI score at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Lid margin thickening grade | Change from baseline Lid margin thickening grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Lid margin notching grade | Change from baseline Lid margin notching grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Lid margin telangiectasia | Change from baseline Lid margin telangiectasia at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| meibomian gland cupping grade | Change from baseline meibomian gland cupping grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Lid meibography grade (upper and lower lid) | Change from baseline Lid meibography grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| meibum expressibility grade | change from baseline meibum expressibility grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| meibum quality grade | Change from baseline meibum quality grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Amount of bacteria culture from lid margin and meibum (colony forming unit) | Change from baseline meibum quality grade at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Tear cytokine level (Interleukin-6, Interferon-gamma, Interleukin-1RA) | Change from baseline Tear cytokine level at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Tear osmole | Change from baseline Tear osmole level at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Schirmer test (not use anaesthesia, mm) | Change from baseline schirmer test at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Tear meniscus height | Change from baseline Tear meniscus height at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| TFLLT (Tear film lipid layer thickness) | Change from baseline TFLLT at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Bulbar conjunctiva hyperaemia (graded by Janvis score) | Change from baseline Bulbar conjunctiva hyperaemia at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Corneal and conjunctiva staining score (Use fluorescent and lissamine green stain) | Change from baseline corneal and conjunctival stain at 1 month after last treatment | 1 month after last treatment (2 month from baseline) | 
| Incidence of adverse event | Incidence of adverse event | at every visit after treatment (baseline, day7, day14, day21) | 
| best spectacle corrected visual acuity (logMAR) | Any change from baseline best spectacle corrected visual acuity (logMAR) at day7, day14, and day 21 | at every visit before treatment (baseline, day7, day14, day21) | 
| uncorrected visual acuity (logMAR) | Any change from baseline uncorrected visual acuity (logMAR) at day7, day14, and day 21 | at every visit before treatment (baseline, day7, day14, day21) | 
| Ocular Surface Index Score scored (OSDI score) | Change from baseline OSDI score at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Lid margin thickening grade | Change from baseline Lid margin thickening grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Lid margin notching grade | Change from baseline Lid margin notching grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Lid margin telangiectasia | Change from baseline Lid margin telangiectasia at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| meibomian gland cupping grade | Change from baseline meibomian gland cupping grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Lid meibography grade (upper and lower lid) | Change from baseline Lid meibography grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| meibum expressibility grade | change from baseline meibum expressibility grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| meibum quality grade | Change from baseline meibum quality grade at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Schirmer test (not use anaesthesia, mm) | Change from baseline schirmer test at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Tear meniscus height | Change from baseline Tear meniscus height at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| TFLLT (Tear film lipid layer thickness) | Change from baseline TFLLT at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Bulbar conjunctiva hyperaemia (graded by Janvis score) | Change from baseline Bulbar conjunctiva hyperaemia at 2 month after last treatment | 2 month after last treatment (3 month from baseline) | 
| Corneal and conjunctiva staining score (Use fluorescent and lissamine green stain) | Change from baseline corneal and conjunctival stain at 2 month after last treatment | 2 month after last treatment (3 month from baseline) |