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

Dry Eye Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06220474
• Other study ID #: 11221686
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: July 31, 2025

Study information

• Verified date: October 2023
• Source: The University of Hong Kong
• Contact: Kendrick Co SHIH
• Phone: 94326271
• Email: kcshih[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: July 31, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 (cloudly 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

Related Conditions & MeSH terms

• Dry Eye Syndromes
• Meibomian Gland Dysfunction

Intervention

Device:
• The Thermage FLX System
The Thermage FLX System is tested for its therapeutic efficacy and safety on treating refractory Meibomian Gland Dysfunction
• Sham treatment
Sham treatment acts as a control to test the therapeutic efficacy and safety of The Thermage FLX System

Locations

Country	Name	City	State
Hong Kong	Grantham Hospital	Hong Kong
Hong Kong	HKU Eye Centre	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (23)

Chia EM, Mitchell P, Rochtchina E, Lee AJ, Maroun R, Wang JJ. Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Clin Exp Ophthalmol. 2003 Jun;31(3):229-32. doi: 10.1046/j.1442-9071.2003.00634.x. — View Citation

Clegg JP, Guest JF, Lehman A, Smith AF. The annual cost of dry eye syndrome in France, Germany, Italy, Spain, Sweden and the United Kingdom among patients managed by ophthalmologists. Ophthalmic Epidemiol. 2006 Aug;13(4):263-74. doi: 10.1080/09286580600801044. — View Citation

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20. — View Citation

Fitzpatrick R, Geronemus R, Goldberg D, Kaminer M, Kilmer S, Ruiz-Esparza J. Multicenter study of noninvasive radiofrequency for periorbital tissue tightening. Lasers Surg Med. 2003;33(4):232-42. doi: 10.1002/lsm.10225. — View Citation

Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf. 2003 Jul;1(3):107-26. doi: 10.1016/s1542-0124(12)70139-8. — View Citation

Gupta PK, Vora GK, Matossian C, Kim M, Stinnett S. Outcomes of intense pulsed light therapy for treatment of evaporative dry eye disease. Can J Ophthalmol. 2016 Aug;51(4):249-253. doi: 10.1016/j.jcjo.2016.01.005. Epub 2016 Jun 22. — View Citation

Hodgkinson DJ. Clinical applications of radiofrequency: nonsurgical skin tightening (thermage). Clin Plast Surg. 2009 Apr;36(2):261-8, viii. doi: 10.1016/j.cps.2008.11.006. — View Citation

Lam PY, Shih KC, Fong PY, Chan TCY, Ng AL, Jhanji V, Tong L. A Review on Evidence-Based Treatments for Meibomian Gland Dysfunction. Eye Contact Lens. 2020 Jan;46(1):3-16. doi: 10.1097/ICL.0000000000000680. — View Citation

Lee AJ, Lee J, Saw SM, Gazzard G, Koh D, Widjaja D, Tan DT. Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia. Br J Ophthalmol. 2002 Dec;86(12):1347-51. doi: 10.1136/bjo.86.12.1347. — View Citation

Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology. 2003 Jun;110(6):1096-101. doi: 10.1016/S0161-6420(03)00262-8. — View Citation

Mathers WD, Lane JA, Zimmerman MB. Tear film changes associated with normal aging. Cornea. 1996 May;15(3):229-34. doi: 10.1097/00003226-199605000-00001. — View Citation

McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology. 1998 Jun;105(6):1114-9. doi: 10.1016/S0161-6420(98)96016-X. — View Citation

Miljanovic B, Dana R, Sullivan DA, Schaumberg DA. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007 Mar;143(3):409-15. doi: 10.1016/j.ajo.2006.11.060. Epub 2007 Jan 2. — View Citation

Moss SE, Klein R, Klein BE. Incidence of dry eye in an older population. Arch Ophthalmol. 2004 Mar;122(3):369-73. doi: 10.1001/archopht.122.3.369. — View Citation

Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol. 2000 Sep;118(9):1264-8. doi: 10.1001/archopht.118.9.1264. — View Citation

Rabensteiner DF, Aminfar H, Boldin I, Schwantzer G, Horwath-Winter J. The prevalence of meibomian gland dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population. Acta Ophthalmol. 2018 Sep;96(6):e707-e711. doi: 10.1111/aos.13732. Epub 2018 Apr 15. — View Citation

Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. doi: 10.1167/iovs.10-6997e. Print 2011 Mar. No abstract available. — View Citation

Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J, Viso E, Vitale S, Jones L. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017 Jul;15(3):334-365. doi: 10.1016/j.jtos.2017.05.003. Epub 2017 Jul 20. — View Citation

Sukal SA, Geronemus RG. Thermage: the nonablative radiofrequency for rejuvenation. Clin Dermatol. 2008 Nov-Dec;26(6):602-7. doi: 10.1016/j.clindermatol.2007.09.007. — View Citation

The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):93-107. doi: 10.1016/s1542-0124(12)70082-4. — View Citation

Toyos R, McGill W, Briscoe D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study. Photomed Laser Surg. 2015 Jan;33(1):41-6. doi: 10.1089/pho.2014.3819. — View Citation

Vegunta S, Patel D, Shen JF. Combination Therapy of Intense Pulsed Light Therapy and Meibomian Gland Expression (IPL/MGX) Can Improve Dry Eye Symptoms and Meibomian Gland Function in Patients With Refractory Dry Eye: A Retrospective Analysis. Cornea. 2016 Mar;35(3):318-22. doi: 10.1097/ICO.0000000000000735. — View Citation

Wang MT, Jaitley Z, Lord SM, Craig JP. Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction. Optom Vis Sci. 2015 Sep;92(9):e321-6. doi: 10.1097/OPX.0000000000000601. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in cornea staining (National Eye Institute Grading System)	This serves as an objective parameter for ocular surface damage, with higher scores meaning worse	from baseline to 6 months post-treatment
Other	Tear osmolarity	This serves as an objective parameter for ocular surface damage	from baseline to 6 months post-treatment
Other	Change in Shirmer's I test reading	In millimetres. Readings serve as objective parameters for tear volume	from baseline to 6 months post-treatment
Other	Tear meniscus height	In millimetres. Readings serve as objective parameters for tear volume	from baseline to 6 months post-treatment
Other	Changes in meiboscore	These readings serve as parameters for meibomian gland dysfunction	from baseline to 6 months post-treatment between study groups
Other	Changes in meibum expressibility	These readings serve as parameters for meibomian gland dysfunction, with higher scores meaning worse	from baseline to 6 months post-treatment between study groups
Other	Changes in meibum quality	These readings serve as parameters for meibomian gland dysfunction, with higher scores meaning worse	from baseline to 6 months post-treatment between study groups
Primary	Change in non-invasive keratographic tear breakup time (NIKBUT)	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	Change in Standard Patient Evaluation of Eye Dryness (SPEED) symptom score	One number was collected per patient, with higher scores meaning worse outcomes	From baseline to 6 months post-treatment between study groups
Secondary	Percentage of subjects with normal non-invasive keratographic tear breakup time (NIKBUT)	> 10 seconds, with lower scores meaning worse	6 months
Secondary	Percentage of subjects with normal SPEED	<5, with higher scores meaning worse	6 months
Secondary	Change in best corrected visual acuity	from logmar(1.0 to -0.1)	from baseline to 6 months post-treatment
Secondary	Incidence of periorbital pain	at least 3/10 and above, with higher scores meaning worse	6 months
Secondary	Incidence of ocular adverse events	evidence of uveitis, conjunctivitis, scleritis/episcleritis, new lens opacities, new cornea opacities	6 months
Secondary	Incidence of non-ocular adverse events	eyelid skin burn, eyelid redness, eyelid hyper/hypopigmentation	6 months