Clinical trial NCT06371300: Photobiomodulation with REd Vs BluE Light (REBEL)
Official title: Photobiomodulation of the Ocular Surface and Eyelids with Different Wavelengths: REd Vs BluE Light (REBEL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dry Eye Syndromes
Meibomian Gland Dysfunction
Blepharitis
Keywords: Low-level light therapy
Lead sponsor: Aston University
Sponsor class: OTHER
First posted: 2024-04-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each participant is randomised to either of 3 groups: Red light only group, red plus blue light group, or sham treatment group.
Primary purpose: TREATMENT

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.

Detailed description: This study will be a randomized, double-masked, exploratory clinical study to assess the potential difference in impact between the two wavelengths used for LLLT. The whole study involves a total of 4 visits (consisting of 3 treatment visits, and 1 follow-up visit). 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)
* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline and 1 month after final treatment session
Secondary outcomes:
measure: Change from Baseline in Visual Acuity to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Blink Rate to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Tear Meniscus Height to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Limbal Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Bacterial Colony to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Blood Flow to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Saponification Grading to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Demodex Presence to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Meibum Expressibility to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Meibum Quality to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Fluorescein Corneal Staining to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Bulbar Conjunctival Staining to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in Meibography Meiboscore to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in MMP-9 Tear Concentration to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
measure: Change from Baseline in LTA Tear Concentration to the Final Follow-up 1 Month After Final Treatment Session
timeFrame: Baseline up to 1 month after final treatment session
Other outcomes:
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.