Therapeutic Efficacy and Safety of Non-Invasive RF Treatment in Refractory MGD

April 24, 2026 updated by: The University of Hong Kong

Therapeutic Efficacy and Safety of Non-Invasive Radiofrequency Treatment in Patients With Refractory Meibomian Gland Dysfunction: A Randomized Controlled Trial

The goal of this prospective, 24-week, double-masked, randomized, sham-controlled clinical trials to compare clinical efficacy and safety of RF and MGX with MGX alone in patients with meibomian gland dysfunction-related dry eye disease. The main question it aims to answer is whether radiofrequency treatment and meibomian gland expression is more effective in improving tear breakup time, as measured using non-invasive video keratography, compared with meibomian gland expression alone, in patients with refractory meibomian gland dysfunction-related dry eye disease.

Participants will be divided into two groups, one group will receive RF treatment followed with MGX and another will receive sham treatment with MGX.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Dry eye disease(DED) is a prevalent age-related ophthalmic condition. Depending on the population studied and the diagnostic criteria used, dry eye disease is estimated to have a high prevalence in most populations , with a female preponderance. In the latest 2017 Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) Epidemiology Report, which compiled dry eye prevalence data from studies worldwide, the reported the prevalence of DED ranged from 5 to 50%. The risk of dry eye disease increases with age, where with every increase in 10 years of age, the self-reported symptoms of DED increased by 2%. In one study in Asia, up to 70% of elderly patients greater than 60 years of age suffering from symptomatic dry eye disease. Dry eye disease causes gritty and painful eyes, with associated blurred vision. For sufferers, it poses a significant burden on quality of life and limitations activities on activities of daily living, resulting in considerable economic costs to society. A 2006 health-economics study in the United Kingdom estimated that the annual healthcare costs to the public sector for every 1000 dry eye patients was USD 1.1 million.

The causes of dry eye can be broadly classified into those with aqueous tear deficiency, excessive tear evaporation or a combination of both. The most common cause of excessive tear evaporation is meibomian gland dysfunction (MGD). This is a common condition of the eyelids where there is a significant change in both the consistency and quantity of meibum, resulting in chronic inflammation of the eyelids and subsequent ocular surface dysfunction. MGD has a prevalence from 46.2% to 69.3% in several studies targeting Asian populations, with a trend of higher prevalence in the elderly. Insufficient lipid secretion from meibomian gland undermines tear film stability, producing dry eye symptoms despite normal tear secretion. In a recent study, up to 70.3% of dry eye patients were found to have concurrent MGD. Refractory MGD is defined by the failure to respond to more than at least three types of conventional therapy, including lubricating eyedrops, gels and ointments and topical or systemic anti-inflammatory treatment, in the past two years.

Currently heat-based therapies are the mainstay and most effective strategies against MGD. Eyelid warming, thermal pulsation and intense light therapy are three prevailing heat-based treatments for MGD- related dry eye disease. Eyelid warming usually involves the application of warm towels, commercialized eye masks (EyeGiene® or Blephasteam®) or eye bags (MGDRx Eye Bag) at least twice a day. Thermal pulsation (Lipiflow®) refers to the delivery of controlled heat together with gentle massage to the eyelids by the machine for 10-17 minutes. Intense pulsed light (IPL) therapy, which uses light energy on the skin surface, is widely used in dermatology to treat a variety of conditions including dermal vascular lesions, such as port wine stains and hemangiomas, facial rosacea, and acne. Each treatment strategy however carries significant limitations. Self-applied eyelid warm compress is cheap and easily available, but when used alone has limited efficacy. Furthermore, sustained patient adherence to treatment is difficult long term. A single treatment of thermal pulsation therapy has been shown to have sustained therapeutic effects up to 12 months after treatment. However, thermal pulsation is not effective in moderate to severe cases of MGD. From existing studies, IPL has greater clinical efficacy than thermal pulsation, but its therapeutic effects are maintained for a significantly shorter period. As such, monthly repeated treatments for up to 8 months may be required for sustained effects. It is also important to note that none of the existing treatments allow the eyelids to evacuate inspissated meibum effectively, with meibum expression by an ophthalmologist an important step in the treatment process. Thus, MGD is likely to recur long-term.

The Thermage FLX System (WA, USA) is a non-ablative radiofrequency (RF) energy-based device, which has been widely adopted in the cosmetic industry for radiofrequency tissue tightening. RF transfers high energy fluences through the skin to deep dermal layers uniformly while protecting the epidermis. It is postulated that RF stimulates subdermal collagen production for tissue tightening effect. There are several advantages of using non-invasive RF treatment over other currently available energy-based devices. Firstly, the Thermage FLX has a much more precise applicator directly targeting the meibomian glands. Thermage FLX addresses both the upper and lower eyelids as close as possible to the lid margin, which is directly where the meibomian glands are situated, it also addresses the tragus area as well, hence a more precise and direct treatment area can be achieved. Secondly, compared to other energy-based devices, Thermage FLX provides a higher accumulative heat transfer effect around the periocular region, due to its repeated application of at least 4-5 cycles around the periorbital region. With higher accumulative heat energy, we anticipate a better and more effective melting of the meibum, which aids in more effective meibum expression. Thirdly, as Thermage FLX has been widely adopted for radiofrequency tissue tightening due to its collagen resynthesis effect, there has been proven improvement of the elasticity of orbicularis and periocular skin tissue, this can promote better blinking effort and better apposition of lid margins. This may enhance the pumping effect of the orbicularis oculi in the long-term. RF treatment is potentially a safe and effective multimodal treatment for MGD-related dry eye disease.

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Kendrick Co SHIH
  • Phone Number: 94326271
  • Email: kcshih@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Grantham Hospital
        • Contact:
          • Kendrick Co Shih
      • Hong Kong, Hong Kong
        • Recruiting
        • HKU Eye Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18 or more
  2. Bilateral dry eye disease as confirmed by presence of both symptoms and signs 2.1 Symptoms: Abnormal result on the Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) dry eye symptom questionnaire (≥5) 2.2 Signs: Abnormal result in at least one of the following three clinical tests - tear osmolarity, NIKBUT and corneal staining for punctate epithelial erosions and,
  3. Bilateral moderate to severe meibomian gland dysfunction - at least Grade 1 meibum quality (cloudy appearance) and Grade 2 meibum expressibility (moderate pressure required). And,
  4. Refractory MGD - The failure to respond to at least three types of conventional therapy, including artificial tears, topical or systemic antibiotics and anti-inflammatory treatments and the aforementioned heat-based therapies, over a period of at least 2 years
  5. Fitzpatrick skin type I-IV - Type V and VI skinned subjects are excluded from the study due to the high risk of pain and focal hypopigmentation
  6. Mentally fit to give informed consent

Exclusion Criteria:

  1. Fitzpatrick skin type V-VI
  2. History of eyelid scarring
  3. Infrared meibography evidence of significant acinar gland atrophy (dropout of >30%) - these patients have been shown not to benefit from heat-based therapies due to end-stage disease
  4. Pregnancy or lactation
  5. Active corneal disease such as infectious keratitis, allergic keratoconjunctivitis, pterygium, exposure keratopathy, lagophthalmos, trichiasis or dellen
  6. Current systemic intake of photosensitive medications, including tetracycline group of drugs.
  7. History of corneal abnormality or surgery within 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiofrequency treatment (RF), followed by meibomian gland expression (MGX)
Before treatment, a thermage return pad will be applied to subject's skin to help prevent electrical burns. The return pad is a rubber, non-active electrode that creates a return path for radiofrequency energy back to the thermage comfort pulse technology (CPT) system. The upper and lower lid of both eyes are marked with skin marking paper (Thermage ® Skin Marking Paper TK-3.00). Coupling fluid is then applied to the external surface of the upper and lower lids of both eyes. All subjects then receive 225 applications to each eye over the upper and lower eyelids. Immediately after treatment, meibomian gland expression will be performed on both upper and lower eyelids of each eye for both eyes of all subjects using meibum expression forceps. Pain is minimized during this procedure by topical application of 0.4% oxybuprocaine hydrochloride.
Device: The Thermage FLX System
The Thermage FLX System is tested for its therapeutic efficacy and safety on treating refractory Meibomian Gland Dysfunction
Sham Comparator: Sham treatment, followed by meibomian gland expression (MGX)
The training mode is used in the Thermage FLX, which simulates treatment without dissipation of radiofrequency energy. Immediately after treatment, meibomian gland expression will be performed on both upper and lower eyelids of each eye for both eyes of all subjects using meibum expression forceps. Pain is minimized during this procedure by topical application of 0.4% oxybuprocaine hydrochloride.
Device: Sham treatment
Sham treatment acts as a control to test the therapeutic efficacy and safety of The Thermage FLX System

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in non-invasive keratographic tear breakup time (NIKBUT)
Time Frame: From baseline to 6 months post- treatment between study groups
NIKBUT is measured in seconds and average of 3 consecutive readings is taken. Higher values mean better outcomes.
From baseline to 6 months post- treatment between study groups

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Standard Patient Evaluation of Eye Dryness (SPEED) symptom score
Time Frame: From baseline to 6 months post-treatment between study groups
One number was collected per patient, with higher scores meaning worse outcomes
From baseline to 6 months post-treatment between study groups
Percentage of subjects with normal non-invasive keratographic tear breakup time (NIKBUT)
Time Frame: 6 months
> 10 seconds, with lower scores meaning worse
6 months
Percentage of subjects with normal SPEED
Time Frame: 6 months
<5, with higher scores meaning worse
6 months
Change in best corrected visual acuity
Time Frame: from baseline to 6 months post-treatment
from logmar(1.0 to -0.1)
from baseline to 6 months post-treatment
Incidence of periorbital pain
Time Frame: 6 months
at least 3/10 and above, with higher scores meaning worse
6 months
Incidence of ocular adverse events
Time Frame: 6 months
evidence of uveitis, conjunctivitis, scleritis/episcleritis, new lens opacities, new cornea opacities
6 months
Incidence of non-ocular adverse events
Time Frame: 6 months
eyelid skin burn, eyelid redness, eyelid hyper/hypopigmentation
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cornea staining (National Eye Institute Grading System)
Time Frame: from baseline to 6 months post-treatment
This serves as an objective parameter for ocular surface damage, with higher scores meaning worse
from baseline to 6 months post-treatment
Tear osmolarity
Time Frame: from baseline to 6 months post-treatment
This serves as an objective parameter for ocular surface damage
from baseline to 6 months post-treatment
Change in Shirmer's I test reading
Time Frame: from baseline to 6 months post-treatment
In millimetres. Readings serve as objective parameters for tear volume
from baseline to 6 months post-treatment
Tear meniscus height
Time Frame: from baseline to 6 months post-treatment
In millimetres. Readings serve as objective parameters for tear volume
from baseline to 6 months post-treatment
Changes in meiboscore
Time Frame: from baseline to 6 months post-treatment between study groups
These readings serve as parameters for meibomian gland dysfunction
from baseline to 6 months post-treatment between study groups
Changes in meibum expressibility
Time Frame: from baseline to 6 months post-treatment between study groups
These readings serve as parameters for meibomian gland dysfunction, with higher scores meaning worse
from baseline to 6 months post-treatment between study groups
Changes in meibum quality
Time Frame: from baseline to 6 months post-treatment between study groups
These readings serve as parameters for meibomian gland dysfunction, with higher scores meaning worse
from baseline to 6 months post-treatment between study groups

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Kendrick Co Shih, The University of Hong Kong, Grantham Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 22, 2024

Primary Completion (Estimated)

October 30, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

December 10, 2023

First Submitted That Met QC Criteria

January 22, 2024

First Posted (Actual)

January 24, 2024

Study Record Updates

Last Update Posted (Actual)

April 27, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11221686

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dry Eye Syndromes

Clinical Trials on The Thermage FLX System

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe