Dry Eye SyndromesNCT06371300
Photobiomodulation With REd vs BluE Light (REBEL)
A study testing Red LLLT and Blue LLLT in people with Dry Eye Syndromes and Meibomian Gland Dysfunction, run by Aston University at 2 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dry Eye Syndromes, Meibomian Gland Dysfunction, Blepharitis
- What is being tested?
- Red LLLT and Blue LLLT
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 May 2024to 30 Dec 2026
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
New Zealand1 site, 1 recruiting
- Recruiting
University of Auckland
Auckland
Jennifer P Craig, PhD, +6493737599 ext. 88173, jp.craig@auckland.ac.nz
United Kingdom1 site
- Completed
Aston Dry Eye Clinic
Birmingham, West Midlands, B4 7ET
About this study
Official title: Photobiomodulation of the Ocular Surface and Eyelids With Different Wavelengths: REd vs BluE Light (REBEL)
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.
Read the 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.
- Conditions
- Dry Eye Syndromes, Meibomian Gland Dysfunction, Blepharitis
- Being tested
- Red LLLT, Blue LLLT, Sham Red LLLT, Sham Blue LLLT
- Keywords
- Low-level light therapy
- Medical subject headings
- Dry Eye Syndromes, Meibomian Gland Dysfunction, Blepharitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red LLLTDevice
Mask with LEDs emitting at wavelengths of 633nm to facial and eyelids region with their eyes closed
Blue LLLTDevice
Mask with LEDs emitting at wavelengths of 428nm to facial and eyelid regions with their eyes closed
Sham Red LLLTDevice
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 LLLTDevice
Mask with LEDs emitting at wavelengths of 428nm, but with <10% fluence power output, to facial and eyelids region with their eyes closed
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Device: Sham Red LLLT; Device: Sham Blue LLLT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
Measured: 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
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.
Measured: 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
Manual subjective count of the number of blinks using the Oculus Keratograph 5M instrument.
Measured: 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
Measure of the volume of tears in mm using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Measure of blood flow using laser doppler flowmetry instrument.
Measured: 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
Measure of saponification on a scale of 0 (no saponification) to 3 (severe saponification)
Measured: 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
Subjective assessment of the amount of Demodex present at the base of the lashes using slit lamp biomicroscopy and white light illumination.
Measured: 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
Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination.
Measured: 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
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.
Measured: Baseline up to 1 month after final treatment session
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.
Measured: Baseline up to 1 month after final treatment session
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.
Measured: Baseline up to 1 month after final treatment session
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.
Measured: Baseline up to 1 month after final treatment session
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.
Measured: Baseline up to 1 month after final treatment session
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.
Measured: Baseline up to 1 month after final treatment session
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).
Measured: Baseline up to 1 month after final treatment session
Change from Baseline in MMP-9 Tear Concentration to the Final Follow-up 1 Month After Final Treatment Session
Measure of matrix metalloproteinase-9 concentration in tears collected with a capillary and measured with a rapid immunoassay test.
Measured: Baseline up to 1 month after final treatment session
Change from Baseline in LTA Tear Concentration to the Final Follow-up 1 Month After Final Treatment Session
Measure of lymphotoxin-A in tears collected with a capillary and measured with a rapid immunoassay test.
Measured: Baseline up to 1 month after final treatment session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2024
- Study start1 May 2024
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Dry Eye SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each participant is randomised to either of 3 groups: Red light only group, red plus blue light group, or sham treatment group.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aston University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James S Wolffsohn, PhD, Study director, Aston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06371300
- Sponsor's protocol ID
- HLS21156
- Status last verified
- Jan 2026
- First submitted
- 15 Apr 2024
- Last updated
- 21 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified datasets will be available upon request.
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.
PubMed 21450918Pult 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.
PubMed 23108007Wolffsohn 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.
PubMed 28736342Schiffman 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.
PubMed 10815152Chalmers 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.
PubMed 20093066Arita 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.
PubMed 27345733