Photobiomodulation With REd vs BluE Light (REBEL)

Official title

Photobiomodulation of the Ocular Surface and Eyelids With Different Wavelengths: REd vs BluE Light (REBEL)

Overview

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.

Interventions

• Device Red LLLT
  Mask with LEDs emitting at wavelengths of 633nm to facial and eyelids region with their eyes closed
• Device Blue LLLT
  Mask with LEDs emitting at wavelengths of 428nm to facial and eyelid regions with their eyes closed
• Device Sham Red LLLT
  Mask with LEDs emitting at wavelengths of 633nm, but with \<10% fluence power output, to facial and eyelids region with their eyes closed
• Device Sham Blue LLLT
  Mask with LEDs emitting at wavelengths of 428nm, but with \<10% fluence power output, to facial and eyelids region with their eyes closed

Primary outcome measures

• Change from Baseline in Bacterial Colony to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]

Secondary outcome measures (12)

• Change from Baseline in Visual Acuity to the Final Follow-up 1 Month After Final Treatment Session [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Limbal Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Blood Flow to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Saponification Grading to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Demodex Presence to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]
• Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 1 Month After Final Treatment Session [Time frame: Baseline up to 1 month after final treatment session]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

New Zealand · 1 center

• University of Auckland — Auckland

United Kingdom · 1 center

• Aston Dry Eye Clinic — Birmingham

Publications

• 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
• 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
• 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
• 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
• 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
• 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

Identifiers

NCT: NCT06371300 · HLS21156

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗