Photobiomodulation With REd vs BluE Light (REBEL)

NCT06371300 | Recruiting

• 1 other identifier: HLS21156
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 2

Brief Summary

The use of photobiomodulation or low-level light therapy (LLLT) in the ophthalmic field stemmed from dermatology which has shown impact on skin blood flow and regeneration. There has been a rise in clinical interest with emerging evidence in the benefits of photobiomodulation in managing chronic inflammatory conditions such as dry eye disease including improvements in ocular discomfort symptoms, tear film stability and tear volume. Despite the observed clinical benefits, limited research has been done to compare photobiomodulation utilising different wavelengths, as most research on dry eye disease has focused on red wavelengths. It has been purported that blue wavelengths may disrupt microbial growth while red wavelengths stimulate energy production and hence increase heat in the affected tissues, although research into these differential impacts at the ocular surface and external eye has been limited. Hence, the aim of this exploratory clinical trial is to compare the impact of using LLLT incorporating red versus blue wavelengths on eyelid haemodynamics and microbiome, as well as conventional ocular surface measures of patients with dry eye disease and blepharitis (inflammation of the eyelids). Participants with dry eye disease, oil gland disruption and blepharitis will receive 3 treatments with these LLLT, each separted by 1 week apart, and followed up to 1 month after the final treatment session. Participants will be randomised to either of 3 groups: Red light only group, Red + Blue light group, or a sham treatment group.

Conditions

Dry Eye Syndromes; Meibomian Gland Dysfunction; Blepharitis

Keywords

Low-level light therapy

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Bacterial Colony to the Final Follow-up 1 Month After Final Treatment Session

  Measure of number of bacterial colonisation obtained from eyelid swabs

  Baseline up to 1 month after final treatment session

Secondary Outcomes (20)

• Change from Baseline in Visual Acuity to the Final Follow-up 1 Month After Final Treatment Session

  Baseline up to 1 month after final treatment session

• Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 1 Month After Final Treatment Session

  Baseline and 1 month after final treatment session

• Change from Baseline in Blink Rate to the Final Follow-up 1 Month After Final Treatment Session

  Baseline up to 1 month after final treatment session

• Change from Baseline in Tear Meniscus Height to the Final Follow-up 1 Month After Final Treatment Session

  Baseline up to 1 month after final treatment session

• Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 1 Month After Final Treatment Session

  Baseline up to 1 month after final treatment session

Study Arms (3)

Red light only group

ACTIVE COMPARATOR

LLLT will be administered using the Espansione Group Ltd Eye-light unit. LLLT consisting of a wearable facial mask with red light emitting diodes (LEDs) is administered for 30 minutes.

Device: Red LLLT

Red plus blue light group

EXPERIMENTAL

LLLT consisting of a wearable facial mask with red LEDs is administered for 15 minutes, followed by a mask with blue LEDs for another 15 minutes.

Device: Red LLLT; Device: Blue LLLT

Sham treatment group

SHAM COMPARATOR

Sham treatment will be administered by using facial mask with red LEDs emitting at less than 10% fluence power output for 15 minutes, followed by a mask with blue LEDs emitting at less than 10% fluence power output for another 15 minutes.

Device: Sham Red LLLT; Device: Sham Blue LLLT

Interventions

Red LLLT DEVICE

Mask with LEDs emitting at wavelengths of 633nm to facial and eyelids region with their eyes closed

Red light only group; Red plus blue light group

Blue LLLT DEVICE

Mask with LEDs emitting at wavelengths of 428nm to facial and eyelid regions with their eyes closed

Red plus blue light group

Sham Red LLLT DEVICE

Mask with LEDs emitting at wavelengths of 633nm, but with \<10% fluence power output, to facial and eyelids region with their eyes closed

Sham treatment group

Sham Blue LLLT DEVICE

Mask with LEDs emitting at wavelengths of 428nm, but with \<10% fluence power output, to facial and eyelids region with their eyes closed

Sham treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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 1 to grade 4 of either eyelid \[Pult and Reide-Pult, 2013\]) will also justify a diagnosis of Meibomian gland dysfunction.
• Individuals will also need to have ocular demodicosis, diagnosed by clinical observation on slit lamp biomicroscope based on signs including collarettes around the base of lashes, visible Demodex tails, or excessive pouting of lash follicles in those with good lid hygiene where Demodex was confirmed by secondary means such as visible Demodex tails.
• Age ≥ 18 years, male or female
• Able to provide written consent in English
• Able to attend a total of 4 visits: 3 treatment visits and followed up for 1 month after final treatment

You may not qualify if:

• Pregnancy
• Ocular light-based therapies including intense pulsed light (IPL) or LLLT treatment within the past 1 month or during study period in addition to those provided in the study
• Contact lens wear in the past 2 weeks or during study period
• Other active ocular surface diseases or history of ocular surgery or corneal infections the past 6 months

Sponsors & Collaborators

• Aston University: lead

Study Sites (2)

University of Auckland

Auckland, New Zealand

RECRUITING

Aston Dry Eye Clinic

Birmingham, West Midlands, B4 7ET, United Kingdom

COMPLETED

Related Publications (6)

• 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.

  PMID: 21450918 BACKGROUND

• 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.

  PMID: 23108007 BACKGROUND

• 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.

  PMID: 28736342 BACKGROUND

• 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.

  PMID: 10815152 BACKGROUND

• 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.

  PMID: 20093066 BACKGROUND

• 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.

  PMID: 27345733 BACKGROUND

MeSH Terms

Conditions

Dry Eye Syndromes; Meibomian Gland Dysfunction; Blepharitis

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Eyelid Diseases

Study Officials

• James S Wolffsohn, PhD

  Aston University

  STUDY DIRECTOR

Central Study Contacts

James S Wolffsohn, PhD

CONTACT

+441212044400; j.chiang@aston.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant is randomised to either of 3 groups: Red light only group, red plus blue light group, or sham treatment group.

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 17, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Deidentified datasets will be available upon request.
• Access Criteria: Deidentified datasets will be available upon request.

Locations

GB (1); NZ (1)