Dry Eye Syndromes, Meibomian Gland Dysfunction
Conditions
Keywords
Intense pulsed light therapy, Low-level light therapy
Brief summary
Dry eye disease is a common condition affecting millions worldwide and costing millions in healthcare due to reduced work productivity and quality of life. The disruption of oil glands in our eyelids known as Meibomian glands, which produce the oily layer of our tears to protect it from evaporating, is one of the most common contributors of dry eye disease. Much effort has been put into developing effective treatments for this condition as new treatments are constantly being introduced to the market. The purpose of this clinical trial is to investigate how proven light-based therapies work in treating dry eye disease and oil gland disruption. These therapies include intense-pulsed light therapy (IPL) which uses a series of light flashes on the facial skin surface, and low-level light therapy (LLLT) which uses a mask with a series of light-emitting diodes (LEDs) to warm the body cells. The main questions it aims to answer are: 1. What are the short- and long-term changes associated with these treatments on the eyelids and surface of the eyes? 2. Does LLLT alone work better than IPL+LLLT in treating dry eye disease and oil gland disruption? Participants with dry eye disease and oil gland disruption will receive four treatments with these light-based therapies each separated by two to three weeks apart, and followed up two to three weeks and three months after the final treatment session. One eye of the participant will receive intense pulsed light together with low-level light therapy, while the other eye will receive only low-level light therapy with a sham intense pulsed light treatment so that the researchers can compare if clinical signs and symptoms improve in one eye more than the other.
Detailed description
This study will be a randomized, double-masked, paired-eye clinical study to assess the potential difference in impact between the two treatment modalities. Each eye of the participant will be randomized to receive either IPL+LLLT or sham IPL+LLLT. The whole study involves a total of 6 visits (consisting of 4 treatment visits, and 2 follow-up visits). All visits will be conducted at the Aston Dry Eye Clinic in Aston University, Birmingham, United Kingdom.
Interventions
DEVICEActual IPL
Five light pulses along lower lid region of one eye of the participant ranging from 59 to 69 Joules (J) over an area of 2.5cm by 4.5cm for each pulse
DEVICESham IPL
Simulated five light pulses along lower lid region of the other eye of the same participant
DEVICELLLT
Mask with LEDs transferring a total of about 32 J/cm\^2 of energy to facial and eyelids region with their eyes closed
Sponsors
Aston University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
One eye of the participant is randomised to receiving IPL and LLLT, while the other eye of the same participant will receive sham intense pulsed light therapy and low-level light therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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) (Wolffsohn et al., 2017) * 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 2 to grade 4 of either eyelid \[Pult and Reide-Pult, 2013\]) will also justify a diagnosis of Meibomian gland dysfunction * Age ≥ 18 years, male or female * Able to provide written consent in English * Able to attend multiple visits (4 treatment visits) and followed up for 2 weeks and 3 months after final treatment
Exclusion criteria
* Pregnancy * Contraindications to IPL treatment (Individuals with darker skin types - Fitzpatrick skin type V or VI, photosensitive epilepsy, tattoos, implants, electrical or acoustic prosthetics, semi-permanent make-up, pigmented lesions or skin cancer in the treatment area, pacemakers, use of photosensitising medication the past 3 months or during treatment period) * Facial or ocular IPL or LLLT treatment within the past 6 months or during study period in addition to those provided in the study * Use of topical medical eyedrops in the past 3 months or during study period * Contact lens wear in the past 2 weeks or during study period * Systemic conditions that can cause dry eye disease or corneal nerve loss including diabetes and Sjögren's syndrome * Other active ocular surface diseases or history of ocular surgery or corneal infections * Individuals with 1 eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session | Baseline and 3 months after final treatment session (up to 6 months after Baseline) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ocular Surface Disease Index Scores to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Validated questionnaire for assessing dry eye symptom severity and impact. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms and impact (Schiffman et al, 2000). |
| Change From Baseline in 5-Item Dry Eye Questionnaire Scores to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 22 with severe dry eye symptoms (Chalmers et al, 2010). |
| Change From Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Measure of the volume of tears in mm using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained. |
| Change From Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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. |
| Change From Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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. |
| Change From Baseline in Total Blinks to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Manual subjective count of the number of total blinks using the Oculus Keratograph 5M instrument. |
| Change From Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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. |
| Change From Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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. |
| Change From Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Subjective grading of the amount of bulbar conjunctival staining using lissamine green instillation, white light illumination and the Oxford grading scale. This ranges from 0 with no staining to 5 with intense staining. |
| Change From Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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 |
| Change From Baseline in Lower Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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). |
| Change From Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Subjective assessment of the amount of Demodex present at the base of the lashes using slit lamp biomicroscopy and white light illumination (Muntz et al, 2020). |
| Change From Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination. |
| Change From Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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 (Arita et al, 2016). |
| Change From Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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 (Tomlinson et al, 2011). |
| Change From Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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 (Tomlinson et al, 2011). |
| Change From Baseline in Total Central Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Measure of total corneal nerve length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. The nerve length is measured using a semi-automated procedure (NeuronJ plugin on ImageJ software) which measures the total length of the corneal nerves in a single frame (400 microns by 400 microns) of corneal confocal microscopy. This is then averaged across three distinct central corneal nerve frame to generate the total central corneal nerve length measure. |
| Change From Baseline in Total Inferior Whorl Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Measure of total inferior whorl length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. The nerve length is measured using a semi-automated procedure (NeuronJ plugin on ImageJ software) which measures the total length of the corneal nerves in a single frame (400 microns by 400 microns) of corneal confocal microscopy. This is conducted for a single frame of the inferior whorl, which is a identifiable landmark where the corneal nerves traverse towards. |
| Change From Baseline in Putative Tissue-Resident Memory T-Cell Density to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Measure of memory T-cell density from sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. |
| Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Frequency Scores to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms. |
| Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Severity Scores to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms. |
| Change From Baseline in Partial Blinks to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Manual subjective count of the number of partial blinks using the Oculus Keratograph 5M instrument. |
| Change From Baseline in Upper Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | 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). |
| Change From Baseline in Putative Dendritic Cell Density to the Final Follow-up 3 Months After Final Treatment Session | Baseline up to 3 months after final treatment session (up to 6 months after Baseline) | Measure of dendritic cell density from sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. |
Countries
United Kingdom
Contacts
STUDY_DIRECTORJames S Wolffsohn, PhD
Aston University
Participant flow
Pre-assignment details
This is a paired eye randomised clinical trial, that is one eye of a participant is randomised to being treated with actual IPL and LLLT, while the other eye of the same participant is randomised to being treated with Sham IPL and LLLT. Hence, 26 participants were recruited, with 26 eyes randomised to having the first treatment, while the contralateral 26 eyes were randomised to the second treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants One eye of the participants were randomly allocated to receving actual IPL and LLLT, while the other eye received sham IPL and LLLT. IPL will be administered using the Espansione Group Ltd Eye-light unit. Five pulses of IPL will be administered along the lower lid region of the eye after the Pult meiboscore and Fitzpatrick skin grading has been entered into the unit. LLLT consisting of a wearable facial mask with red LEDs is then administered for 15 minutes.
Actual IPL: Five light pulses along lower lid region of one eye of the participant ranging from 59 to 69 Joules (J) over an area of 2.5cm by 4.5cm for each pulse.
Sham IPL: Simulated five light pulses along lower lid region of the other eye of the same participant
LLLT: Mask with LEDs transferring a total of about 32 J/cm\^2 of energy to facial and eyelids region with their eyes closed | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 17.5 |
| Existing dry eye interventions Eyelid cleansers | 2 Participants |
| Existing dry eye interventions Lubricating eyedrops, gel or ointment | 19 Participants |
| Existing dry eye interventions Warm compresses | 3 Participants |
| Fitzpatrick skin type (I to IV) I | 1 Participants |
| Fitzpatrick skin type (I to IV) II | 14 Participants |
| Fitzpatrick skin type (I to IV) III | 5 Participants |
| Fitzpatrick skin type (I to IV) IV | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 15 Participants |
| Race/Ethnicity, Customized East Asian | 3 Participants |
| Race/Ethnicity, Customized Mixed | 2 Participants |
| Race/Ethnicity, Customized South Asian | 4 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 5 Participants |
| Systemic comorbidities Arthritis | 1 Participants |
| Systemic comorbidities Asthma | 1 Participants |
| Systemic comorbidities Hypercholesterolaemia | 2 Participants |
| Systemic comorbidities Hypertension | 3 Participants |
| Systemic comorbidities Hypothyroidism | 2 Participants |
| Systemic comorbidities Raynaud's phenonemon | 1 Participants |
| Systemic comorbidities Vitamin B12 deficiency | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change From Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months 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.
Time frame: Baseline and 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session | -2.61 seconds |
| Sham IPL and LLLT | Change From Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session | -0.85 seconds |
Secondary
Change From Baseline in 5-Item Dry Eye Questionnaire Scores to the Final Follow-up 3 Months After Final Treatment Session
Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 22 with severe dry eye symptoms (Chalmers et al, 2010).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in 5-Item Dry Eye Questionnaire Scores to the Final Follow-up 3 Months After Final Treatment Session | -3.29 score on a scale |
| Sham IPL and LLLT | Change From Baseline in 5-Item Dry Eye Questionnaire Scores to the Final Follow-up 3 Months After Final Treatment Session | -3.29 score on a scale |
Secondary
Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Frequency Scores to the Final Follow-up 3 Months After Final Treatment Session
Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Frequency Scores to the Final Follow-up 3 Months After Final Treatment Session | -21.63 score on a scale |
| Sham IPL and LLLT | Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Frequency Scores to the Final Follow-up 3 Months After Final Treatment Session | -20.54 score on a scale |
Secondary
Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Severity Scores to the Final Follow-up 3 Months After Final Treatment Session
Validated questionnaire for assessing dry eye symptom severity and frequency. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Severity Scores to the Final Follow-up 3 Months After Final Treatment Session | -18.54 score on a scale |
| Sham IPL and LLLT | Change From Baseline in Adapted Symptom Assessment Questionnaire in Dry Eye Severity Scores to the Final Follow-up 3 Months After Final Treatment Session | -16.75 score on a scale |
Secondary
Change From Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months 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.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session | 0.05 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session | -0.12 units on a scale |
Secondary
Change From Baseline in Demodex Presence to the Final Follow-up 3 Months 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 (Muntz et al, 2020).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session | -0.04 count of lashes with Demodex |
| Sham IPL and LLLT | Change From Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session | -0.17 count of lashes with Demodex |
Secondary
Change From Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months 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.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session | -0.46 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session | -0.29 units on a scale |
Secondary
Change From Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months 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 (Arita et al, 2016).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session | -0.33 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session | -0.29 units on a scale |
Secondary
Change From Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months 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.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session | 0.54 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session | 0.38 units on a scale |
Secondary
Change From Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session
Subjective grading of the amount of bulbar conjunctival staining using lissamine green instillation, white light illumination and the Oxford grading scale. This ranges from 0 with no staining to 5 with intense staining.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session | -0.42 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session | -0.29 units on a scale |
Secondary
Change From Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months 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
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session | 0.31 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session | 0.15 units on a scale |
Secondary
Change From Baseline in Lower Lid Meibography Meiboscore to the Final Follow-up 3 Months 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).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Lower Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | -0.08 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Lower Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | 0.08 units on a scale |
Secondary
Change From Baseline in Meibum Expressibility to the Final Follow-up 3 Months 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 (Tomlinson et al, 2011).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session | -0.35 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session | -0.50 units on a scale |
Secondary
Change From Baseline in Meibum Quality to the Final Follow-up 3 Months 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 (Tomlinson et al, 2011).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session | -0.07 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session | 0.08 units on a scale |
Secondary
Change From Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session
Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session | 0 blocked or capped meibomian glands |
| Sham IPL and LLLT | Change From Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session | 0 blocked or capped meibomian glands |
Secondary
Change From Baseline in Ocular Surface Disease Index Scores to the Final Follow-up 3 Months After Final Treatment Session
Validated questionnaire for assessing dry eye symptom severity and impact. Scores range from 0 indicating no dry eye symptoms to 100 with severe dry eye symptoms and impact (Schiffman et al, 2000).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Ocular Surface Disease Index Scores to the Final Follow-up 3 Months After Final Treatment Session | -11.34 score on a scale |
| Sham IPL and LLLT | Change From Baseline in Ocular Surface Disease Index Scores to the Final Follow-up 3 Months After Final Treatment Session | -11.34 score on a scale |
Secondary
Change From Baseline in Partial Blinks to the Final Follow-up 3 Months After Final Treatment Session
Manual subjective count of the number of partial blinks using the Oculus Keratograph 5M instrument.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Partial Blinks to the Final Follow-up 3 Months After Final Treatment Session | -2.04 count of partial blinks |
| Sham IPL and LLLT | Change From Baseline in Partial Blinks to the Final Follow-up 3 Months After Final Treatment Session | -2.04 count of partial blinks |
Secondary
Change From Baseline in Putative Dendritic Cell Density to the Final Follow-up 3 Months After Final Treatment Session
Measure of dendritic cell density from sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Putative Dendritic Cell Density to the Final Follow-up 3 Months After Final Treatment Session | 1.24 cells/mm^2 |
| Sham IPL and LLLT | Change From Baseline in Putative Dendritic Cell Density to the Final Follow-up 3 Months After Final Treatment Session | 0.98 cells/mm^2 |
Secondary
Change From Baseline in Putative Tissue-Resident Memory T-Cell Density to the Final Follow-up 3 Months After Final Treatment Session
Measure of memory T-cell density from sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Putative Tissue-Resident Memory T-Cell Density to the Final Follow-up 3 Months After Final Treatment Session | -0.65 cells/mm^2 |
| Sham IPL and LLLT | Change From Baseline in Putative Tissue-Resident Memory T-Cell Density to the Final Follow-up 3 Months After Final Treatment Session | -4.95 cells/mm^2 |
Secondary
Change From Baseline in Tear Meniscus Height to the Final Follow-up 3 Months 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.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session | 0.03 mm |
| Sham IPL and LLLT | Change From Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session | 0.05 mm |
Secondary
Change From Baseline in Total Blinks to the Final Follow-up 3 Months After Final Treatment Session
Manual subjective count of the number of total blinks using the Oculus Keratograph 5M instrument.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Total Blinks to the Final Follow-up 3 Months After Final Treatment Session | -0.96 count of total blinks |
| Sham IPL and LLLT | Change From Baseline in Total Blinks to the Final Follow-up 3 Months After Final Treatment Session | -0.96 count of total blinks |
Secondary
Change From Baseline in Total Central Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session
Measure of total corneal nerve length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. The nerve length is measured using a semi-automated procedure (NeuronJ plugin on ImageJ software) which measures the total length of the corneal nerves in a single frame (400 microns by 400 microns) of corneal confocal microscopy. This is then averaged across three distinct central corneal nerve frame to generate the total central corneal nerve length measure.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Total Central Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | -0.76 mm/mm^2 |
| Sham IPL and LLLT | Change From Baseline in Total Central Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | 0.18 mm/mm^2 |
Secondary
Change From Baseline in Total Inferior Whorl Nerve Length to the Final Follow-up 3 Months After Final Treatment Session
Measure of total inferior whorl length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy. The nerve length is measured using a semi-automated procedure (NeuronJ plugin on ImageJ software) which measures the total length of the corneal nerves in a single frame (400 microns by 400 microns) of corneal confocal microscopy. This is conducted for a single frame of the inferior whorl, which is a identifiable landmark where the corneal nerves traverse towards.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Total Inferior Whorl Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | -2.15 mm/mm^2 |
| Sham IPL and LLLT | Change From Baseline in Total Inferior Whorl Nerve Length to the Final Follow-up 3 Months After Final Treatment Session | -0.15 mm/mm^2 |
Secondary
Change From Baseline in Upper Lid Meibography Meiboscore to the Final Follow-up 3 Months 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).
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Upper Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | 0 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Upper Lid Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session | 0 units on a scale |
Secondary
Change From Baseline in Visual Acuity to the Final Follow-up 3 Months 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.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session | -0.02 units on a scale |
| Sham IPL and LLLT | Change From Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session | 0.002 units on a scale |
Other Pre-specified
Change From Baseline in Blood Perfusion of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
Measure of blood flow using laser doppler flowmetry instrument, with higher values indicating better perfusion.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Blood Perfusion of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -1.03 arbitrary units (AU) |
| Sham IPL and LLLT | Change From Baseline in Blood Perfusion of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -1.65 arbitrary units (AU) |
Other Pre-specified
Change From Baseline in Fluorescence Measures of Flavins of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
Measure of the amount of flavins, specifically flavin adenine dinucleotide, within the lower eyelid cutaneous skin.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Fluorescence Measures of Flavins of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -18.64 arbitrary units (AU) |
| Sham IPL and LLLT | Change From Baseline in Fluorescence Measures of Flavins of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -7.64 arbitrary units (AU) |
Other Pre-specified
Change From Baseline in Fluorescence Measures of NADH of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
Measure of the amount of nicotinamide-adenine dinucleotide within the lower eyelid cutaneous skin, with higher values indicating increased nicotinamide-adenine dinucleotide content.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Fluorescence Measures of NADH of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -0.47 arbitrary units (AU) |
| Sham IPL and LLLT | Change From Baseline in Fluorescence Measures of NADH of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -9.12 arbitrary units (AU) |
Other Pre-specified
Change From Baseline in Microvasculature Blood Oxygen Saturation of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
Measure of saturation of oxygen in the blood of the lower eyelid measured using tissue oximetry.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Microvasculature Blood Oxygen Saturation of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | 0.98 percentage of saturation |
| Sham IPL and LLLT | Change From Baseline in Microvasculature Blood Oxygen Saturation of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | 4.33 percentage of saturation |
Other Pre-specified
Change From Baseline in Optical Redox Ratio of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
The fluorescence intensity ratio between NADH and FAD used as a diagnostic parameter.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Optical Redox Ratio of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | 0.28 ratio |
| Sham IPL and LLLT | Change From Baseline in Optical Redox Ratio of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | -0.16 ratio |
Other Pre-specified
Change From Baseline in Relative Erythrocyte Fraction Volume of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session
Measure of tissue oximetry for the the percentage of red blood cells in the total volume of blood.
Time frame: Baseline up to 3 months after final treatment session (up to 6 months after Baseline)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Actual IPL and LLLT | Change From Baseline in Relative Erythrocyte Fraction Volume of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | 0.22 percentage of RBC in blood |
| Sham IPL and LLLT | Change From Baseline in Relative Erythrocyte Fraction Volume of Lower Eyelid to the Final Follow-up 3 Months After Final Treatment Session | 1.29 percentage of RBC in blood |