None listed
Conditions
Brief summary
Dry eye affects 20% adults and imparts substantial economic burden, however there is a limited understanding of the complex mechanisms underlying dry eye disease, particularly immune-mediated processes, and how inflammation might be optimally modulated to achieve therapeutic control of the condition. ‘Light therapy’ has recently emerged as a potential non-invasive treatment for dry eye. In particular, low-level light therapy, using light emitting diodes (LEDs), has been developed with the rationale of modifying relevant biological processes, such as increasing cellular metabolism with production of heat within the eyelids. This is proposed to improve the flow of oil (known as meibum) into the tears, from specialised oil (meibomian) glands in the eyelids. These glands are often dysfunctional in dry eye disease, an associated condition known as meibomian gland dysfunction (MGD). While these treatments are being rapidly adopted in practice, there remains a lack of evidence on the impact of ‘light therapy’ on ocular inflammation and/or the immune cell populations at the ocular surface. The primary purpose of this study is to characterise the in vivo features of human corneal immune cells when exposed to different coloured light stimuli (red vs blue) used in low-level light therapy in the treatment of dry eye associated with MGD.
Interventions
The study interventions comprise low-level light therapy delivered via a clinical device (Eye-light, Espansione Group, Italy) used for treating dry eye. This device is TGA-approved (ARTG listing number 326014), and intended for the treatment of dry eye syndrome by targeting the meibomian glands around the eyelids. Facial masks, which contain a series of light emitting diodes (LEDs), are used to deliver the treatment in-office for 15 minutes over a course of four visits, each 7±3 days apart. Part
The study interventions comprise low-level light therapy delivered via a clinical device (Eye-light, Espansione Group, Italy) used for treating dry eye. This device is TGA-approved (ARTG listing number 326014), and intended for the treatment of dry eye syndrome by targeting the meibomian glands around the eyelids. Facial masks, which contain a series of light emitting diodes (LEDs), are used to deliver the treatment in-office for 15 minutes over a course of four visits, each 7±3 days apart. Participants will be seated or lying down comfortably for the duration of the treatment. Participants will be randomised into one of three treatment groups (red light therapy [633 nm wavelength], blue light therapy [428 nm wavelength], and inactive control therapy [sham red or sham blue light]). A researcher not involved with performing the clinical assessments will develop a randomisation schedule using a randomisation table created by computer software (i.e., computerised sequence generation) for the study intervention (1:1:1), and also a separate randomisation (1:1) sub-schedule for sham red or sham blue light intervention for those sub-randomised to the inactive control therapy group. The randomisation schedules will be concealed in sealed envelopes until a study researcher designated as a treatment administrator unseals the envelope before the first treatment at Visit 2. A session attendance checklist will be used to monitor exposure to intervention for each participant. Corneal imaging will also be done immediately after the first treatment (Visit 2) to assess for the short-term impact(s) of low-level light therapy, and before the second treatment (Visit 3), third treatment (Visit 4) and fourth treatment (Visit 5) to assess the longitudinal effects of a course of treatment. A 1-month post-treatment follow-up visit (Visit 6) will also be conducted to assess for any potential extended impacts.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant inclusion criteria at the screening evaluation visit (Visit 1): 1. Male or female aged at least 18, with full legal capacity to volunteer; 2. Provide written informed consent to participate; 3. Can understand and follow study instructions, with the intention of completing all required study visits; 4. Have typical sleeping patterns, defined generally as obtaining at least 6 hours of sleep per night, with sleep onset time between 21:00 PM and 2:00 AM, and waking up between 05:00 AM and 09:00 AM, by self-report; 5. Have at least 3 T cells in either the whorl or inferior cornea within the imaging field of view on in vivo confocal microscopy (IVCM); 6. Be sufficiently proficient in English to understand the study details, instructions, and answer questions from the study researcher, and the study questionnaires; 7. Has not worn contact lenses consistently (i.e., more than once per week) over the 3 months prior, and not anticipated throughout their participation in the study; 8. Has clinically significant dry eye disease, as defined by the TFOS DEWS III definition, involve dry eye symptoms (i.e., an Ocular Surface Disease Index (OSDI) [full version] score greater than or equal to 13, out of 100, AND at least one of the following clinical signs: a. Tear osmolarity of more than or equal to 308 mOsm/L in either eye or an interocular difference greater than 8 mOsm/L; b. NITBUT < 10 sec in either eye; c. Ocular surface staining: > 5 corneal spots with fluorescein, > 9 conjunctival spots with lissamine green, or eyelid margin staining (more than or equal to 2 mm length and more than or equal to 25% width) with lissamine green 9. Has meibomian gland dysfunction (MGD), defined by a meibomian gland score (MGS) of less than or equal to 12.
Exclusion criteria
Exclusion criteria at the screening evaluation visit (Visit 1): 1. Any active ocular disease and/or infection (besides dry eye disease and MGD) that might significantly affect corneal immune cells or nerves; 2. A clinically significant injury to either eye in the past 12 weeks; 3. Ocular surgery within the past six months, or ocular surgery is planned over the course of participation in the study; 4. Prior history of laser refractive eye surgery; 5. A known allergy to, or previous reaction to, any eye drops required for the study; 6. The presence of cancer in the required treatment area for the low-level light therapy (e.g. basal cell carcinoma, squamous cell carcinoma and/or melanoma of the facial skin); 7. Photosensitivity to red or blue light, or a history of light-induced nervous system disorders such as epilepsy or migraine, by self-report; 8. Current use of photosensitising medications (such as doxycycline, Roaccutane), or anticipated use over the course of participation in the study, by self-report; 9. Presence of non-removable metallic piercings in the periocular and malar regions; 10. Unwilling to avoid wearing excessive make-up, eyelash extensions or removable metallic piercings at the treatment area to avoid interference with the light therapy during treatment sessions (at Visit 2, Visit 3, Visit 4 and Visit 5); 10. Presence of significant corneal scarring or a physical factor that impairs the ability to perform corneal imaging; 11. Current or recent use (within the last 30 days) of any topical medications other than artificial lubricant eye drops (e.g., anti-allergy eye drops, anti-glaucoma medications, corticosteroids) or systemic corticosteroids or immunomodulatory medications, or anticipated use over the course of participation in the study; 12. Anticipated change in non-heat based, self-administered eyelid hygiene regimen over the course of the study (Note: Participants must have had a stable regimen for at least 30 days prior to Visit 1), by self-report; 13. A history of using warm eye compresses 30 days prior, or anticipated use over the course of participation in the study, by self-report; 14. A history of receiving Lipiflow or similar treatments, or light-based therapies including intense pulsed light therapy and low-level light therapy, on the facial regions within 6 months prior, or anticipated use over the course of participation in the study, by self-report; 15. A history of a systemic infection known to affect corneal immune status (e.g., positive for COVID-19 or upper respiratory infection within the past four weeks), by self-report; 16. A systemic condition (e.g., Sjogren’s disease, diabetes or other) that affects corneal immune status; 17. Has received a vaccination in the past two weeks, by self-report; 18. An infectious blood-borne illness, such as hepatitis or human immunodeficiency virus (HIV), that may affect the eyes, by self-report; 19. Females who are pregnant or breastfeeding, or who plan to become pregnant during the study, by self-report; 20. Unable to sit/lie supine comfortably during the examination procedures; 21. Participation in an interventional clinical trial within the previous 30 days, or currently enrolled in an interventional clinical trial; 22. Current shiftwork and/or recent cross-time zone travel in the last month, or such anticipated travel during the study period; 23. A condition or situation that, in the opinion of the study investigator, will limit the potential participant’s ability to comply with the study protocol, might adversely affect their safety or substantially confound the study outcomes.
Outcome results
None listed