Clinical trial NCT04608942: Refractory Meibomian Gland Dysfunction and Plasma Jet
Official title: Plasma Jet Approach for Refractory Meibomian Gland Dysfunction Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Meibomian Gland Dysfunction
Dry Eye Disease
Evaporative Dry Eye
Inflammation
Tear Film Deficiency
Keywords: meibomian gland dysfunction (MGD)
evaporative dry eye disease (E-DED)
jett plasma medical lift
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
First posted: 2020-10-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PURPOSE: The investigators propose a new treatment for refractory Meibomian Gland Dysfunction (MGD) patients with plasma jet to remove the hyperkeratinization layer from the lid margin to unblock terminal gland ducts and use thermal stimulation to enhance meibum delivery.

METHODS: A prospective, interventional clinical safety and efficacy trial with 25 patients from the Department of Ophthalmology at Escola Paulista de Medicina (UNIFESP) to determine the efficacy and safety of the treatment of refractory MGD patients with plasma jet on both upper and lower lids. Patients will be submitted to an ophthalmology workup with best-corrected visual acuity (BCVA) (ETDRS chart) and dry eye questionnaires (DEQ-5 and OSDI). Bulbar redness, tear film meniscus height, noninvasive breakup time (NIKBUT), meibography under infrared light will be measured with Keratograph (Oculus®). Following, tear film osmolarity (i-PenTM), meibomian gland expression, and Marx line assessment. All exams were performed at the baseline, 30 days, and 90 days after the plasma jet application.

Detailed description: INTRODUCTION Dry eye disease (DED) is one of the most prevalent conditions at an ophthalmology office that may reach 15 to 40% of prevalence in the population. It is didactically classified as two forms that exist as a continuum: aqueous deficient dry eye (ADDE) and evaporative dry eye (EDE). In EDE patients Meibomian Gland Dysfunction (MGD) is the major etiology in which the insufficient meibum secretion can be decreased by cicatricial (trachoma, ocular pemphigoid, erythema multiforme) and non-cicatricial causes (skin disorders such as acne rosacea and atopic dermatitis, blepharitis).

MGD pathophysiology can be explained by hyposecretion or ducts obstruction, resulting in low delivery of phospholipids and cholesterol that grant stability to the tear film. Hyposecretion of the sebaceous glands can result from intrinsic (age, ethnicity, hormonal profile) and extrinsic factors (chronic blepharitis, Demodex folliculorum infestation, contact lens wear, topical drops). Furthermore, the duct obstruction occurs in a consequence to cicatricial rearrangement of the terminal ducts or by non-cicatricial hyperkeratinization of the lid margins, leading to increased duct pressure, dilatation, and disuse atrophy of the glands.

Questionnaires such as Ocular Surface Disease Index (OSDI) and Dry Eye Questionnaire-5 (DEQ-5) that evaluate the grade of severity of DED and assessment of MGD by noninvasive tear breakup time (BUT) evaluation that measures tear film stability and by meibography under infrared light that analyses gland vitality are central when dealing with any EDE patient.

The treatment of MGD can be very challenging in cases where a clinical approach with non-preserved ocular lubricants, lid hygiene, and warm compresses are not sufficient. Oral tetracyclines can be a good alternative in cases of evident lid inflammation to reduce bacterial colonization and inhibit collagenase action although long-term use intolerance limits its use.

Thermodynamic treatment with a device that performs controlled local heating and massage of the ducts showed clinical improvement and symptoms reduction whereas multiple sessions are necessary. Mechanical debridement of gland ducts terminals with scalpel blade also improved ocular symptoms and gland function of patients with EDE with MGD. A combination of intense pulsed light (IPL) therapy and gland expression has been shown to be an effective treatment to MGD with increases in BUT and improvement of ocular symptoms related to DED.

Plasma jet has been successfully used in Dermatology and is an increasingly popular method for smoothing wrinkles, blunt blepharoplasty, as well as performing thermal ablation for superficial skin layers.

The investigators propose a new treatment for refractory MGD patients with plasma jet with a device used in Dermatology to remove the hyperkeratinization layer from the lid margin to unblock terminal gland ducts and use thermal stimulation to enhance meibum delivery.

METHODS A prospective, interventional clinical safety and efficacy trial to determine the efficacy and safety of the treatment of refractory MGD patients with plasma jet will be conducted at Ophthalmology Department at Escola Paulista de Medicina (UNIFESP) with 25 Caucasian patients.

All patients will be instructed about the study design and will be given full access to the results at any time of the protocol. All will sign an informed consent form and have their identity protected in accordance with patient medical confidentiality. This case series is in accordance with Good Clinical Practices and the Declaration of Helsinki.

Patients will be submitted to an ophthalmology workup with best-corrected visual acuity (BCVA) (ETDRS chart), dry eye questionnaires (DEQ-5 and OSDI), corneal topography, bulbar redness, tear meniscus height, noninvasive breakup time (NBUT), tear film osmolarity, meibography under infrared light, meibomian gland expression and Marx line assessment. All exams will be performed before and 30 days after the plasma jet application.

Patients will be instructed about the procedure by the ophthalmologist and a nurse and the procedure will be performed after topical anesthesia with lidocaine 2.0%. The plasma jet will be applied 3 times on both superior and inferior terminal gland ducts in the lid margins with a 14.4mm tip and intensity of 5 on the device (0,9W) reaching only the superficial epidermis. Patients will receive topical antibiotics and corticosteroids after the procedure. During all periods (90 days) patients will use sodium hyaluronate 0,15% and actinoquinol at the recommended dosage of twice a day.

The software program GraphPad Prism version 7.0 will be used to conduct the statistical analyses. Continuous data distribution will be verified by the Kolmogorov-Smirnov normality test. Data will be analyzed by the Kruskal-Wallis test with the Wilcoxon test considering 2-time points for nonparametric variables and paired t-test for parametric variables. All p values of \< 0.05 will indicate statistically significant differences.

Eligibility criteria: Inclusion Criteria:

* Refractory meibomian gland dysfunction;
* Previous eyelid hygiene with warm compress in the last 6 months;
* Previous oral intake of antibiotics and antiinflammatories in the last 6 months;
* Previous oral tetracycline treatment for at least one month in the last 6 months;
* DEQ-5 score greater than 6;
* OSDI score greater than 13;
* Tear film osmolarity greater than 308mOsm or a difference between eyes greater than 8 mOsm;
* Meibomian gland expression greater than 8;
* Meibomian gland expression grades 2 or 3 \[Nelson 1930\];

Exclusion Criteria:

* Cardiac pacemaker or ECG Holter;
* Other electromagnetic device implanted;
* Epilepsy;
* Pregnancy;
* Metal implants in the periocular area;
* Skin diseases in the periocular area;
* Systemic inflammatory diseases;
* Oncological diseases;
* Allergy to local anesthetics;

Primary outcomes:
measure: Dry Eye Questionnaire (DEQ-5)
timeFrame: 30 days
measure: Ocular Surface Disease Index (OSDI)
timeFrame: 30 days
measure: Bulbar redness
timeFrame: 30 days
measure: Tear film meniscus height
timeFrame: 30 days
measure: Non-invasive tear breakup time (NITBUT)
timeFrame: 30 days
measure: Tear film osmolarity
timeFrame: 30 days
measure: Meibomian gland expression
timeFrame: 30 days
Secondary outcomes:
measure: Dry Eye Questionnaire (DEQ-5)
timeFrame: 90 days
measure: Ocular Surface Disease Index (OSDI)
timeFrame: 90 days
measure: Bulbar redness
timeFrame: 90 days
measure: Tear film meniscus height
timeFrame: 90 days
measure: Non-invasive tear breakup time (NITBUT)
timeFrame: 90 days
measure: Tear film osmolarity
timeFrame: 90 days
measure: Meibomian gland expression
timeFrame: 90 days
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Departamento de Oftalmologia da Escola Paulista de Medicina - UNIFESP
state: SP
city: Sao Paulo
country: Brazil
facility: Department of Ophthalmology, UNIFESP&EPM
state: SP
Study officials:
affiliation: Associate Professor in Ophthalmology (Federal University of Sao Paulo - UNIFESP)
name: Rossen M Hazarbassanov, MD PhD
role: PRINCIPAL_INVESTIGATOR
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