Clinical trial NCT05577910: Vectored Thermal Pulsation, Intense Pulsed Light, and Eyelid Warm Compress Therapies for MGD
Official title: Vectored Thermal Pulsation, Intense Pulsed Light, and Eyelid Warm Compress (VIEW) Therapies for Meibomian Gland Dysfunction- a Randomized, Assessor-masked, Active-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Meibomian Gland Dysfunction
Keywords: Meibomian Gland Dysfunction
Dry Eye Disease
Vectored Thermal Pulsation therapy
Intense Pulsed Light therapy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-10-13
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 most meibomian gland dropout (meiboscore), fewest expressible meibomian glands, thinnest lipid layer, or lowest TFBUT values (in this order) will be selected as the study eye.

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

Topical lubricating eye drops (Hypromellose, 3mg/ml) will be the monotherapy for all subjects.
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Change from baseline Tear film breakup time (TFBUT) at 6 months
timeFrame: 6 months
measure: Change from baseline Tear film breakup time (TFBUT) at 15 months
timeFrame: 15 months
Secondary outcomes:
measure: Change in Ocular Surface Disease Index (OSDI)
timeFrame: 15 months
measure: Change in Standard Patient Evaluation of Eye Dryness (SPEED)
timeFrame: 15 months
measure: Change in symptom Assessment iN Dry Eye (SANDE)
timeFrame: 15 months
measure: Change in ocular comfort index (OCI)
timeFrame: 15 months
measure: Change in dry eye questionnaire (DEQ-5)
timeFrame: 15 months
measure: Change in tear film breakup time (TFBUT)
timeFrame: 15 months
measure: Change in non-invasive keratograph break-up time (NIKBUT)
timeFrame: 15 months
measure: Change in bulbar conjunctival hyperaemia
timeFrame: 15 months
measure: Change in lower tear meniscus height (TMH)
timeFrame: 15 months
measure: Change in lipid layer thickness (LLT)
timeFrame: 15 months
measure: Change in tear interferometric fringe pattern
timeFrame: 15 months
measure: Change in meiboscore
timeFrame: 15 months
measure: Change in meibograde
timeFrame: 15 months
measure: Change in partial blinking rate
timeFrame: 15 months
measure: Change in schirmer's test (ST)
timeFrame: 15 months
measure: Change in Lid margin and eyelash abnormalities
timeFrame: 15 months
measure: Change in corneal and conjunctival staining score
timeFrame: 15 months
measure: Change in lid wiper epitheliopathy (LWE)
timeFrame: 15 months
measure: Change in expressibility of meibomian glands in the meibomian glands yielding liquid secretion (MGYLS) (the inferior eyelid)
timeFrame: 15 months
measure: Change in expressibility of meibomian glands in proportion of meibomian orifices yielding lipid secretions (the inferior eyelid))
timeFrame: 15 months
measure: Change in quality of expressed meibum
timeFrame: 15 months
Other outcomes:
measure: Change in visual acuity
timeFrame: 15 months
measure: Levels in procedure-related pain (VAS)
timeFrame: 3 months
measure: Change in intraocular pressure
timeFrame: 15 months
measure: Change in lens opacity
timeFrame: 15 months
measure: Change in anterior chamber activities
timeFrame: 15 months
measure: Number of participants with iris defect and transillumination
timeFrame: 15 months
measure: Number of participants with abnormalities of fundus
timeFrame: 15 months
measure: Number of participants with loss of lashes and eyebrows
timeFrame: 15 months
measure: Number of participants with facial redness
timeFrame: 15 months
measure: Number of participants with facial swelling
timeFrame: 15 months
measure: Number of participants with facial bruises
timeFrame: 15 months
measure: Number of participants with facial pigmentation
timeFrame: 15 months
measure: Change of α-diversity in ocular surface microbiome
timeFrame: 15 months
measure: Change of β-diversity in ocular surface microbiome
timeFrame: 15 months
measure: Gene expression profiles
timeFrame: Baseline
Locations:
city: Kowloon
country: Hong Kong
facility: The Chinese University of Hong Kong Eye Centre (CUHKEC)
city: Kowloon
country: Hong Kong
facility: Hong Kong Eye Hospital
city: Shatin
country: Hong Kong
facility: The CUHK Medical Centre (CUHKMC)
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: The Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong
name: Kelvin KL Chong, MBChB
role: PRINCIPAL_INVESTIGATOR
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