Refractory Meibomian Gland Dysfunction and Plasma Jet

Sponsor
Federal University of São Paulo (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04608942
Collaborator
(none)
25
Enrollment
2
Locations
2
Arms
33.6
Anticipated Duration (Months)
12.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Device: Jett Plasma Medical Lift
  • Procedure: Mechanical Debridement
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
25 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Plasma Jet Approach for Refractory Meibomian Gland Dysfunction Patients
Actual Study Start Date :
Nov 11, 2019
Actual Primary Completion Date :
Aug 7, 2020
Anticipated Study Completion Date :
Aug 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Jett Plasma Medical Lift Application

In the study group, the plasma jet will be applied to the superior and inferior eyelid margin in both eyes.

Device: Jett Plasma Medical Lift
Plasma Application versus Mechanical Debridement in refractory meibomian gland dysfunction

Active Comparator: Mechanical Debridement

In the control group, the mechanical debridement of the superior and inferior eyelid margin with a scalpel blade will be performed.

Procedure: Mechanical Debridement
Plasma Application versus Mechanical Debridement in refractory meibomian gland dysfunction

Outcome Measures

Primary Outcome Measures

  1. Dry Eye Questionnaire (DEQ-5) [30 days]

    Dry Eye Questionnaire (DEQ-5) comprises of 5 quick questions and its score ranges from 0 to 22, with lower scores indicating a less severe disease (improvement).

  2. Ocular Surface Disease Index (OSDI) [30 days]

    Ocular Surface Disease Index (OSDI) comprises of 12 questions, each one scored from 0 to 4, and the final score, on a scale from 0 to 100, result from the sum of all values divided by the number of questions answered. Lower scores indicate a less severe disease (improvement).

  3. Bulbar redness [30 days]

    Conjunctival hyperemia will be measured with Keratograph (Oculus®, Inc). This software grades de hyperemia in both nasal and temporal bulbar regions and in the limbal area, with a final score indicating overall ocular surface redness. Greater scores indicate greater hyperemia.

  4. Tear film meniscus height [30 days]

    Tear film meniscus height will be measured with Keratograph (Oculus®, Inc). This software allows individual measurente of the tear film meniscus height (in milimeters) that will be performed in three regions (nasal, central and temporal tear meniscus) and the arithmetic average will be considered to evaluate treatment outcomes, with increased heights indicanting more tear volume.

  5. Non-invasive tear breakup time (NITBUT) [30 days]

    Non-invasive tear breakup time (NITBUT) will be assessed first with Keratograph (Oculus®, Inc). The NITBUT evaluate the tear film stability by registering the time lapse for the first rupture in the tear film to appear. Greater values indicates a more stable tear film.

  6. Tear film osmolarity [30 days]

    Tear film osmolarity will be measured by collecting a micro drop from the tear meniscus with i-Pen (i-Med Pharma, Inc). The tear osmolarity is used to indirect assess occular surface inflammation, with tear osmolalities greater than 308 mOsm or a difference between eyes greater than 8 mOsm indicating tear film disturbance (Dry Eye WorkShop II - DEWS II 2017).

  7. Meibomian gland expression [30 days]

    Meibomian gland expression will be performed using Meibomian Gland Evaluator (MGE), a special devide with precise pression, that will allow to assess meibomian glands in the slit lamp. This devices acts on five glands at a time, so meibum deliverance can be judged in quantity (is there any gland duct obstructed?) and quality (is meibum clear, cloudy or opaque?).

Secondary Outcome Measures

  1. Dry Eye Questionnaire (DEQ-5) [90 days]

    Dry Eye Questionnaire (DEQ-5) comprises of 5 quick questions and its score ranges from 0 to 22, with lower scores indicating a less severe disease (improvement).

  2. Ocular Surface Disease Index (OSDI) [90 days]

    Ocular Surface Disease Index (OSDI) comprises of 12 questions, each one scored from 0 to 4, and the final score, on a scale from 0 to 100, result from the sum of all values divided by the number of questions answered. Lower scores indicate a less severe disease (improvement).

  3. Bulbar redness [90 days]

    Conjunctival hyperemia will be measured with Keratograph (Oculus®, Inc). This software grades de hyperemia in both nasal and temporal bulbar regions and in the limbal area, with a final score indicating overall ocular surface redness. Greater scores indicate greater hyperemia.

  4. Tear film meniscus height [90 days]

    Tear film meniscus height will be measured with Keratograph (Oculus®, Inc). This software allows individual measurente of the tear film meniscus height (in milimeters) that will be performed in three regions (nasal, central and temporal tear meniscus) and the arithmetic average will be considered to evaluate treatment outcomes, with increased heights indicanting more tear volume.

  5. Non-invasive tear breakup time (NITBUT) [90 days]

    Non-invasive tear breakup time (NITBUT) will be assessed first with Keratograph (Oculus®, Inc) and then with florescein dye. The NITBUT evaluate the tear film stability by registering the time lapse for the first rupture in the tear film to appear. Greater values indicates a more stable tear film.

  6. Tear film osmolarity [90 days]

    Tear film osmolarity will be measured by collecting a micro drop from the tear meniscus with i-Pen (i-Med Pharma, Inc). The tear osmolarity is used to indirect assess occular surface inflammation, with tear osmolalities greater than 308 mOsm or a difference between eyes greater than 8 mOsm indicating tear film disturbance (Dry Eye WorkShop II - DEWS II 2017).

  7. Meibomian gland expression [90 days]

    Meibomian gland expression will be performed using Meibomian Gland Evaluator (MGE), a special devide with precise pression, that will allow to assess meibomian glands in the slit lamp. This devices acts on five glands at a time, so meibum deliverance can be judged in quantity (is there any gland duct obstructed?) and quality (is meibum clear, cloudy or opaque?).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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;

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Departamento de Oftalmologia da Escola Paulista de Medicina - UNIFESPSao PauloSPBrazil04023 062
2Department of Ophthalmology, UNIFESP&EPMSao PauloSPBrazil

Sponsors and Collaborators

  • Federal University of São Paulo

Investigators

  • Principal Investigator: Rossen M Hazarbassanov, MD PhD, Associate Professor in Ophthalmology (Federal University of Sao Paulo - UNIFESP)

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Rossen Mihaylov Hazarbassanov, MD, PhD, Associate Professor in Ophthalmology, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT04608942
Other Study ID Numbers:
  • 31031420.6.0000.5505
First Posted:
Oct 30, 2020
Last Update Posted:
Oct 30, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Rossen Mihaylov Hazarbassanov, MD, PhD, Associate Professor in Ophthalmology, Federal University of São Paulo
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 30, 2020