Clinical trial NCT06004895: Mechanisms of Light-based Therapies for Dry Eye Disease
Official title: Mechanisms of Action of Light-based Therapies in the Management of Dry Eye Disease and Meibomian Gland Dysfunction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Dry Eye Syndromes
Meibomian Gland Dysfunction
Keywords: Intense pulsed light therapy
Low-level light therapy
Lead sponsor: Aston University
Sponsor class: OTHER
First posted: 2023-08-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One eye of the participant is randomised to receiving IPL and LLLT, while the other eye of the same participant will receive sham intense pulsed light therapy and low-level light therapy.
Primary purpose: TREATMENT

Brief summary: Dry eye disease is a common condition affecting millions worldwide and costing millions in healthcare due to reduced work productivity and quality of life. The disruption of oil glands in our eyelids known as Meibomian glands, which produce the oily layer of our tears to protect it from evaporating, is one of the most common contributors of dry eye disease. Much effort has been put into developing effective treatments for this condition as new treatments are constantly being introduced to the market.

The purpose of this clinical trial is to investigate how proven light-based therapies work in treating dry eye disease and oil gland disruption. These therapies include intense-pulsed light therapy (IPL) which uses a series of light flashes on the facial skin surface, and low-level light therapy (LLLT) which uses a mask with a series of light-emitting diodes (LEDs) to warm the body cells. The main questions it aims to answer are:

1. What are the short- and long-term changes associated with these treatments on the eyelids and surface of the eyes?
2. Does LLLT alone work better than IPL+LLLT in treating dry eye disease and oil gland disruption?

Participants with dry eye disease and oil gland disruption will receive four treatments with these light-based therapies each separated by two to three weeks apart, and followed up two to three weeks and three months after the final treatment session. One eye of the participant will receive intense pulsed light together with low-level light therapy, while the other eye will receive only low-level light therapy with a sham intense pulsed light treatment so that the researchers can compare if clinical signs and symptoms improve in one eye more than the other.

Detailed description: This study will be a randomized, double-masked, paired-eye clinical study to assess the potential difference in impact between the two treatment modalities. Each eye of the participant will be randomized to receive either IPL+LLLT or sham IPL+LLLT. The whole study involves a total of 6 visits (consisting of 4 treatment visits, and 2 follow-up visits). All visits will be conducted at the Aston Dry Eye Clinic in Aston University, Birmingham, United Kingdom.

Eligibility criteria: Inclusion Criteria:

* Individuals with dry eye disease symptoms (Ocular Surface Disease Index questionnaire (OSDI) score ≥ 13 or Dry Eye Questionnaire (DEQ5) score \> 6) and signs (tear film instability measured with non-invasive tear break-up time \< 10 s or ocular surface damage measured using special dyes placed on the front surface of the eyes that temporarily stains any aggravated or damaged cells: \> 5 corneal spots, \> 9 conjunctival spots or lid margin staining ≥ 2mm in length and ≥ 25% in width) (Wolffsohn et al., 2017)
* Individuals need to also have Meibomian gland dysfunction. The diagnosis of Meibomian gland dysfunction depends on how many of 5 glands in the central lower eyelid can express oil, and the quality of the oil. A diagnosis is made if there is decreased expressibility (grade 1-3 on the Pflugfelder scale) and reduced quality of oil (grade 1-3 on Bron scale). Any presence of gland blockage and/or loss of oil glands grade 2 to grade 4 of either eyelid \[Pult and Reide-Pult, 2013\]) will also justify a diagnosis of Meibomian gland dysfunction
* Age ≥ 18 years, male or female
* Able to provide written consent in English
* Able to attend multiple visits (4 treatment visits) and followed up for 2 weeks and 3 months after final treatment

Exclusion Criteria:

* Pregnancy
* Contraindications to IPL treatment (Individuals with darker skin types - Fitzpatrick skin type V or VI, photosensitive epilepsy, tattoos, implants, electrical or acoustic prosthetics, semi-permanent make-up, pigmented lesions or skin cancer in the treatment area, pacemakers, use of photosensitising medication the past 3 months or during treatment period)
* Facial or ocular IPL or LLLT treatment within the past 6 months or during study period in addition to those provided in the study
* Use of topical medical eyedrops in the past 3 months or during study period
* Contact lens wear in the past 2 weeks or during study period
* Systemic conditions that can cause dry eye disease or corneal nerve loss including diabetes and Sjögren's syndrome
* Other active ocular surface diseases or history of ocular surgery or corneal infections
* Individuals with 1 eye

Primary outcomes:
measure: Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline and 3 months after final treatment session
Secondary outcomes:
measure: Change from Baseline in Ocular Surface Disease Index scores to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in 5-Item Dry Eye Questionnaire scores to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Blink Rate to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Total Central Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Total Inferior Whorl Nerve Length to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Immune Cell Density to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Frequency Scores to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
measure: Change from Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Severity Scores to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
Other outcomes:
measure: Change from Baseline in Blood Flow to the Final Follow-up 3 Months After Final Treatment Session
timeFrame: Baseline up to 3 months after final treatment session
Locations:
city: Birmingham
country: United Kingdom
facility: Aston Dry Eye Clinic
state: West Midlands
Study officials:
affiliation: Aston University
name: James S Wolffsohn, PhD
role: STUDY_DIRECTOR
References:
citation: Tomlinson A, Bron AJ, Korb DR, Amano S, Paugh JR, Pearce EI, Yee R, Yokoi N, Arita R, Dogru M. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2006-49. doi: 10.1167/iovs.10-6997f. Print 2011 Mar. No abstract available.
citation: Pult H, Riede-Pult B. Comparison of subjective grading and objective assessment in meibography. Cont Lens Anterior Eye. 2013 Feb;36(1):22-7. doi: 10.1016/j.clae.2012.10.074. Epub 2012 Oct 27.
citation: Wolffsohn JS, Arita R, Chalmers R, Djalilian A, Dogru M, Dumbleton K, Gupta PK, Karpecki P, Lazreg S, Pult H, Sullivan BD, Tomlinson A, Tong L, Villani E, Yoon KC, Jones L, Craig JP. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017 Jul;15(3):539-574. doi: 10.1016/j.jtos.2017.05.001. Epub 2017 Jul 20.
citation: Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001/archopht.118.5.615.
citation: Chalmers RL, Begley CG, Caffery B. Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): Discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses. Cont Lens Anterior Eye. 2010 Apr;33(2):55-60. doi: 10.1016/j.clae.2009.12.010. Epub 2010 Jan 25.
citation: Arita R, Minoura I, Morishige N, Shirakawa R, Fukuoka S, Asai K, Goto T, Imanaka T, Nakamura M. Development of Definitive and Reliable Grading Scales for Meibomian Gland Dysfunction. Am J Ophthalmol. 2016 Sep;169:125-137. doi: 10.1016/j.ajo.2016.06.025. Epub 2016 Jun 23.