Vectored Thermal Pulsation, Intense Pulsed Light, and Eyelid Warm Compress Therapies for MGD

NCT ID: NCT05577910

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-08
• Study Completion Date: 2025-06-30

Brief Summary

Meibomian gland dysfunction (MGD), closely associated with Dry Eye Disease (DED), is a chronic condition where terminal ducts are obstructed and/or glandular secretion changes. The efficacy of traditional treatment options, e.g. eyelid warm compress therapy (EW) is limited with low compliance. This study aims to (1)compare the efficacy and safety of two emerging alternatives- vectored thermal pulsation(VTP) or intense pulsed light and meibomian gland expression(IPL + MGX) with EW therapy; (2)identify factors predicting outcome.

This is a prospective, randomized, assessor-masked, active-controlled clinical study. 360 participants (360 study eyes) with mild-to-moderate MGD will be randomized by minimization into three arms equally, receiving either VTP by TearScience-LipiFlow® Thermal Pulsation System (month 0), IPL by Lumenis®️M22 with MGX (month 0, 1, 2, 3) or EW (twice daily). Lubricating eye drops (3% Hypromellose) will be provided for all subjects throughout the study period(15 months). Tear film breakup time will be assessed as primary outcome at month 6, 15. Serial measurements of MG, tear-film, DED-related parameters, intraocular pressure, compliance to EW, factors associated with outcomes and treatment-related complications will be conducted at baseline and each follow-up visit by masked observers at baseline and eight follow-up evaluation (month 0, 1, 2, 3, 4, 6, 9, 12, 15).

Detailed Description

Dry eye disease (DED) is an emerging, under-recognized and under-treated epidemic of the 21st century. It is one of the commonest reasons seeking eye consultation worldwide. Depending on the diagnostic criteria, geographic location and population concerned, prevalence of DED ranges from 30 to over 50% in the Asia Pacific regions compared to around 5-10% in the United States. Up to 90% of DED is closely associated with meibomian gland dysfunction (MGD), a chronic and progressive condition characterized by terminal duct obstruction, qualitative and/or quantitative changes in the glandular secretions (meibum) which causes tear instability by increasing tear evaporation and subsequently increased tear osmolarity, ocular surface inflammation, epithelial damage and ocular surface disease. Studies suggest that MGD affects between 5-20 % of Caucasians and over 60% of Asians populations.

Conventional treatments for MGD including self-administered eyelid hygiene, eyelid warm compress therapy (EW), artificial tears, including lipid-containing lubricants are limited in their efficacies for moderate to advanced disease. Prescription medications (topical steroids, topical and oral antibiotics, topical immunomodulatory agents e.g. cyclosporine and oral omega-3 essential fatty acids) have demonstrated efficacies in improving symptoms and signs of MGD; however side-effects including preservative-related adverse events, development of antibiotic resistance, cost, accessibility, off-label use, and the need for ongoing treatments often limit their long-term use.

Despite the described range of available options, management for MGDs is often considered unsatisfactory and frustrating by clinicians and patients. Compliance to long-term, home-based self-administered therapies is known to be suboptimal while practitioner-administered treatment including meibomian gland expression (MGX) provides transient relief.

Intense pulsed light (IPL) therapy is widely used in cosmetic dermatology as well as therapeutically for a wide range of skin conditions with favourable efficacy and tolerability. Concurrent MGD improvements were observed serendipitously in patients undergoing IPL for rosacea. With growing interest in combining IPL+MGX as practitioner-administered physical therapy for MGD, recent review and meta-analysis showed its effectiveness and safety while calling to investigate its effect beyond 6 months after the last IPL treatment.

Vectored thermal pulsation (VTP) is approved by FDA as another practitioner-administered physical therapy for MGD. The device covers both the cutaneous and mucosal surfaces of the eyelids; the rear portion of the device provides heat to the MG, and the front portion gives mechanical stimulation to the eyelid skin. It evacuates the MG of the upper and lower eyelids simultaneously with minimal discomfort while protecting the cornea, rendering the experience for patients generally favorable. Recent meta-analysis showed that a single 12-minute VTP was more efficacious than EW in treating MGD.

Knowledge gaps:

Level I evidence comparing efficacies between two promising practitioner-administered therapies VTP and multi-session IPL+MGX with standard self-administered twice-daily EW for MGD is currently lacking. The onset and offset of therapeutic effects, time course of multi-session IPL+MGX, single-session VTP or twice-daily EW on MGD up to 15-month post-treatment initiation or 12-month post last session of IPL have not been studied either in an RCT setting. These important gaps will be addressed in this application.

Primary Objective:

To compare the efficacy and safety of 1-session vectored thermal pulsation (VTP) or 4-session intense pulsed light and meibomian gland expression (IPL+MGX) with twice-daily eyelid warm compress (EW) therapy for meibomian gland dysfunction (MGD).

Secondary Objectives:

1. To compare the course of MGD among groups over 15 months (12-month after final IPL+MGX);

2. To identify factors predicting responses and compliance to therapies.

Hypotheses:

1. Both 1-session VTP and 4-session IPL+MGX are more efficacious than twice-daily EW in improving MGD;

2. MGD improves earlier after VTP;

3. MGD improvement lasts longer after 4-session IPL+MGX.

Study design:

This is a prospective, randomized, assessor-masked, 3-arm (1:1:1), active-controlled trial of 360 subjects with meibomian gland dysfunction contributing one study eye. For subjects with both eyes eligible, the eye with the fewest quality of expressed meibum, thinnest lipid layer, or the lowest TFBUT values (in this order) will be selected as the study eye.

A total of 360 patients with symptomatic MGD will be recruited from the participating hospitals coordinated by the Chinese University of Hong Kong (CUHK) Research Clinic, the CUHK Eye Centre (CUHKEC), Department of Ophthalmology and Visual Science, Faculty of Medicine, The CUHK.

Randomization will be carried out by a computer-generated minimization program. Minimization is a dynamic process to reduce the imbalance between trial arms with respect to a range of predefined prognostic variables, and a randomization schedule is therefore not drawn up in advance. A form describing the baseline characteristics of each subject according to these minimization criteria: gender, age, and quality of expressed meibum from the study eye. Treatment allocation will be sent to the unmasked trial coordinator for arrangement at baseline (month 0).

Enrolled patients will be randomized into one of the following groups, 1 month after recruitment during the 15-month study period receiving bilateral treatment of:

Group A: 1-session VTP at month 0; Group B: 4-session IPL+MGX at month 0,1,2,3; Group C: twice daily EW for 15 months.

All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used as frequently as needed from recruitment to study exit (total 16 months).

IPL or VTP is given by unmasked treating investigators not involved in data collection. Follow-up investigators collecting the data are masked to participants' treatment assignment. This information can be disclosed upon request after the completion of the study. Unmasked trial coordinators will ensure masking by reminding and accompanying each patient before and during visit. Treatment-related complications will be evaluated by all participants in a standard datasheet regardless of group assignment. Follow-up investigators will be asked if they know each participant's group assignment at each visit and why.

Tear film breakup time will be assessed as the primary outcome (month 6 and 15). Serial measurements of MG, tear-film, DED-related parameters, intraocular pressure, compliance to EW, factors associated with outcomes, and treatment-related complications will be conducted by masked investigators at baseline and eight follow-up evaluations (month 0, 1, 2, 3, 4, 6, 9, 12, 15).

Conditions

Meibomian Gland Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group A

One session VTP at month 0.

Group Type: EXPERIMENTAL

Vectored thermal pulsation (VTP) therapy

Intervention Type: DEVICE

VTP purchased from TearScience®️ is an automated thermal pulsation system that is designed to heat and simultaneously evacuate the meibomian gland contents. It is performed by the unmasked treating investigators as described by the equipment manufacturer. In brief, one to two drops of topical anesthesia are applied prior to the bilateral application of the activators. The inner portion of the activator applies a constant temperature of 42.5°C to the tarsal conjunctiva of upper and lower eyelids. Simultaneously, the outer portion of the activator applies directional, pulsatile pressure to the external eyelid surfaces (maximum 6 psi) for the 12-minute treatment cycle. Participants will receive one session of VTP treatment only (month 0).

Topical eye drops (Hypromellose, 3mg/ml)

Intervention Type: DRUG

All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used as frequently as needed from recruitment to study exit (total 16 months).

Group B

Four sessions IPL+MGX at month 0,1,2,3.

Group Type: EXPERIMENTAL

Intense pulsed light with meibomian gland expression (IPL+MGX) therapy

Intervention Type: DEVICE

IPL is delivered using the proprietary "dry eye mode" setting of the Lumenis®️ M22TM system per the Toyos protocol. Pulse intensity (11-14 J/cm2) is inversely related to the Fitzpatrick skin phototype of each participant and will be used for the same patient throughout the study. IPL will be delivered to four overlapping zones inferior to each eye and a fifth pulse applied temporally adjacent to the lateral canthus four times. Both eyelids are closed and sealed with IPL-Aid disposable eye shields. MGX is immediately performed on both upper and lower eyelids of each eye and pain will be minimized by topical anesthetic. Participants will receive four-session IPL and MGX treatment (month 0, 1, 2 ,3).

Topical eye drops (Hypromellose, 3mg/ml)

Intervention Type: DRUG

All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used as frequently as needed from recruitment to study exit (total 16 months).

Group C

Twice daily EW for 15 months.

Group Type: ACTIVE_COMPARATOR

Eyelid Warm Compress Therapy (EW)

Intervention Type: BEHAVIORAL

EW using warm wet towel to each eye is performed twice daily for 10 mins. A treatment diary will be given for patients randomized to EW for daily recording which will be reviewed and recorded by the unmasked study coordinator at each study visit.

Topical eye drops (Hypromellose, 3mg/ml)

Intervention Type: DRUG

All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used as frequently as needed from recruitment to study exit (total 16 months).

Interventions

Vectored thermal pulsation (VTP) therapy

VTP purchased from TearScience®️ is an automated thermal pulsation system that is designed to heat and simultaneously evacuate the meibomian gland contents. It is performed by the unmasked treating investigators as described by the equipment manufacturer. In brief, one to two drops of topical anesthesia are applied prior to the bilateral application of the activators. The inner portion of the activator applies a constant temperature of 42.5°C to the tarsal conjunctiva of upper and lower eyelids. Simultaneously, the outer portion of the activator applies directional, pulsatile pressure to the external eyelid surfaces (maximum 6 psi) for the 12-minute treatment cycle. Participants will receive one session of VTP treatment only (month 0).

Intervention Type: DEVICE

Intense pulsed light with meibomian gland expression (IPL+MGX) therapy

IPL is delivered using the proprietary "dry eye mode" setting of the Lumenis®️ M22TM system per the Toyos protocol. Pulse intensity (11-14 J/cm2) is inversely related to the Fitzpatrick skin phototype of each participant and will be used for the same patient throughout the study. IPL will be delivered to four overlapping zones inferior to each eye and a fifth pulse applied temporally adjacent to the lateral canthus four times. Both eyelids are closed and sealed with IPL-Aid disposable eye shields. MGX is immediately performed on both upper and lower eyelids of each eye and pain will be minimized by topical anesthetic. Participants will receive four-session IPL and MGX treatment (month 0, 1, 2 ,3).

Intervention Type: DEVICE

Eyelid Warm Compress Therapy (EW)

EW using warm wet towel to each eye is performed twice daily for 10 mins. A treatment diary will be given for patients randomized to EW for daily recording which will be reviewed and recorded by the unmasked study coordinator at each study visit.

Intervention Type: BEHAVIORAL

Topical eye drops (Hypromellose, 3mg/ml)

All patients will be given one single topical lubricant (Hypromellose, 3mg/ml) to be used as frequently as needed from recruitment to study exit (total 16 months).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥18 years of age with no upper age limit;

2. Agree to attend follow-up visits and comply to treatment regimen;

3. Symptomatic dry eye TFBUT (average of 3 times) ≤ 5 seconds and OSDI ≥ 13;

4. Mild to moderate (level 3-4) MGD on at least one eye;

5. Fitzpatrick skin type 1-4.

Exclusion Criteria

1. Contact lens wear 3 months before or during the study period;

2. Use of topical (including anti-glaucomatous, cyclosporin, antibiotics) or systemic medication known to affect (worsen or improve) MGD 3 months before or during the study period;

3. Major systemic (e.g. Sjogren's syndrome), dermatologic (e.g. Rosacea) known to affect MGD or ocular conditions (including thyroid eye disease, recurrent conjunctivitis, ocular allergies);

4. Ocular procedures (excluding uncomplicated cataract operation) 3 months before and any ocular procedure during the study period;

5. History of vision correction surgery or plan to undergo the procedure during the study period;

6. Dermatological treatment (including chemical peeling, laser, IPL or energy device in the periocular and facial region) 6 months before or during the study period;

7. Contraindications to IPL therapy (including recent sun-burn, photosensitivity, active or pigmented skin lesions, cancer, implants, tattoos, semi-permanent makeup in the periocular area);

8. Contraindications to VTP therapy (ocular surgery, ocular injury, ocular herpes of eye or eyelid, and ocular inflammation 3 months before the study; active ocular infection, etc.)

9. Women who are pregnant, nursing, planning pregnancy, or of childbearing potential not using a reliable method of contraception.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Kelvin Kam-lung Chong, MD

Associate Professor, Department of Ophthalmology and Visual Sciences, CUHK

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kelvin KL Chong, MBChB

Role: PRINCIPAL_INVESTIGATOR

The Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong

Locations

Hong Kong Eye Hospital

Kowloon, Hong Kong, Hong Kong

The Chinese University of Hong Kong Eye Centre (CUHKEC)

Kowloon, , Hong Kong

The CUHK Medical Centre (CUHKMC)

Shatin, , Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Countries

Hong Kong

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Other Identifiers

HMRF-08190266

Identifier Type: -

Identifier Source: org_study_id