Photobiomodulation With REd vs BluE Light (REBEL)

Dry Eye Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06371300
• Other study ID #: HLS21156
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2024
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Aston University
• Contact: Jeremy Chung Bo Chiang, PhD
• Phone: +441212043934
• Email: j.chiang[@]aston.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: December 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Blepharitis
• Dry Eye Syndromes
• Meibomian Gland Dysfunction

Intervention

Device:
• Red LLLT
Mask with LEDs emitting at wavelengths of 633nm to facial and eyelids region with their eyes closed
• Blue LLLT
Mask with LEDs emitting at wavelengths of 428nm to facial and eyelid regions with their eyes closed
• 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
• 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

Locations

Country	Name	City	State
United Kingdom	Aston Dry Eye Clinic	Birmingham	West Midlands

Sponsors (1)

Lead Sponsor	Collaborator
Aston University

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 1 Month After Final Treatment Session	Measure of the stability of tears and how fast the tears evaporate in seconds using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained.	Baseline and 1 month after final treatment session
Secondary	Change from Baseline in Visual Acuity to the Final Follow-up 1 Month After Final Treatment Session	Subjective measure of visual acuity using Logarithm of the Minimum Angle Resolution (logMAR) scoring, ranging from -0.30 which signify the ability to be able to resolve the smallest letters, to 1.00 which signify the ability to resolve only the largest letters	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Blink Rate to the Final Follow-up 1 Month After Final Treatment Session	Manual subjective count of the number of blinks using the Oculus Keratograph 5M instrument.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Tear Meniscus Height to the Final Follow-up 1 Month After Final Treatment Session	Measure of the volume of tears in mm using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the appearance of the lipid layer pattern as a surrogate measure of its thickness using the Oculus Keratograph 5M instrument. This ranges from Grade 1 indicating very thin lipid layer to Grade 6 indicating very thick lipid layer.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session	Automated objective grading of the bulbar conjunctival redness using the Oculus Keratograph 5M instrument. This ranges from Grade 0 indicating no redness to Grade 4 indicating substantial redness.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Limbal Conjunctival Hyperaemia to the Final Follow-up 1 Month After Final Treatment Session	Automated objective grading of the limbal conjunctival redness using the Oculus Keratograph 5M instrument. This ranges from Grade 0 indicating no redness to Grade 4 indicating substantial redness.	Baseline up to 1 month after final treatment session
Secondary	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	Change from Baseline in Blood Flow to the Final Follow-up 1 Month After Final Treatment Session	Measure of blood flow using laser doppler flowmetry instrument.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Saponification Grading to the Final Follow-up 1 Month After Final Treatment Session	Measure of saponification on a scale of 0 (no saponification) to 3 (severe saponification)	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Demodex Presence to the Final Follow-up 1 Month After Final Treatment Session	Subjective assessment of the amount of Demodex present at the base of the lashes using slit lamp biomicroscopy and white light illumination.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 1 Month After Final Treatment Session	Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the amount of telangiectasia at the lid margins using slit lamp biomicroscopy and white light illumination. This grading ranges from 0 with no telangiectasia to 3 with severe telangiectasia.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Meibum Expressibility to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of meibum expressibility of lower eyelids using slit lamp biomicroscopy and white light illumination. This grading ranges from 0 with all glands being expressible to 3 with no glands being expressible.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Meibum Quality to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of meibum quality of lower eyelids using slit lamp biomicroscopy and white light illumination. This grading ranges from 0 with clear fluid being expressed to 3 with inspissated toothpaste-like expression.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Fluorescein Corneal Staining to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the amount of corneal staining using fluorescein instillation, cobalt blue light illumination and the Oxford grading scale. This ranges from 0 with no staining to 5 with intense staining.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Bulbar Conjunctival Staining to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the amount of bulbar conjunctival staining using fluorescein and lissamine green instillation, white light illumination and the Oxford grading scale. This ranges from 0 with no staining to 5 with intense staining.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the amount of lid wiper epitheliopathy using lissamine green instillation and white light illumination. This grading ranges from 0 with no lid wiper epitheliopathy to 4 with severe lid wiper epitheliopathy.	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Meibography Meiboscore to the Final Follow-up 1 Month After Final Treatment Session	Subjective grading of the amount of Meibomian gland loss using infrared imaging and the Pult meiboscore. This grading ranges from 0 with no gland loss to 4 with severe gland loss (Pult and Reide-Pult, 2013).	Baseline up to 1 month after final treatment session
Secondary	Change from Baseline in Total Corneal Nerve Length to the Final Follow-up 1 Month After Final Treatment Session	Measure of total corneal nerve length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy.	Baseline up to 1 month after final treatment session