xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06004895</url>
    </required_header>
    <id_info>
      <org_study_id>HLS21118</org_study_id>
      <nct_id>NCT06004895</nct_id>
    </id_info>
    <brief_title>Mechanisms of Light-based Therapies for Dry Eye Disease</brief_title>
    <acronym>MOLT</acronym>
    <official_title>Mechanisms of Action of Light-based Therapies in the Management of Dry Eye Disease and Meibomian Gland Dysfunction</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aston University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aston University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Dry eye disease is a common condition affecting millions worldwide and costing millions in&#xD;
        healthcare due to reduced work productivity and quality of life. The disruption of oil glands&#xD;
        in our eyelids known as Meibomian glands, which produce the oily layer of our tears to&#xD;
        protect it from evaporating, is one of the most common contributors of dry eye disease. Much&#xD;
        effort has been put into developing effective treatments for this condition as new treatments&#xD;
        are constantly being introduced to the market.&#xD;
  &#xD;
        The purpose of this clinical trial is to investigate how proven light-based therapies work in&#xD;
        treating dry eye disease and oil gland disruption. These therapies include intense-pulsed&#xD;
        light therapy (IPL) which uses a series of light flashes on the facial skin surface, and&#xD;
        low-level light therapy (LLLT) which uses a mask with a series of light-emitting diodes&#xD;
        (LEDs) to warm the body cells. The main questions it aims to answer are:&#xD;
  &#xD;
          1. What are the short- and long-term changes associated with these treatments on the&#xD;
             eyelids and surface of the eyes?&#xD;
  &#xD;
          2. Does LLLT alone work better than IPL+LLLT in treating dry eye disease and oil gland&#xD;
             disruption?&#xD;
  &#xD;
        Participants with dry eye disease and oil gland disruption will receive four treatments with&#xD;
        these light-based therapies each separated by two to three weeks apart, and followed up two&#xD;
        to three weeks and three months after the final treatment session. One eye of the participant&#xD;
        will receive intense pulsed light together with low-level light therapy, while the other eye&#xD;
        will receive only low-level light therapy with a sham intense pulsed light treatment so that&#xD;
        the researchers can compare if clinical signs and symptoms improve in one eye more than the&#xD;
        other.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study will be a randomized, double-masked, paired-eye clinical study to assess the&#xD;
        potential difference in impact between the two treatment modalities. Each eye of the&#xD;
        participant will be randomized to receive either IPL+LLLT or sham IPL+LLLT. The whole study&#xD;
        involves a total of 6 visits (consisting of 4 treatment visits, and 2 follow-up visits). All&#xD;
        visits will be conducted at the Aston Dry Eye Clinic in Aston University, Birmingham, United&#xD;
        Kingdom.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <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.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline and 3 months after final treatment session</time_frame>
      <description>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.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Ocular Surface Disease Index scores to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in 5-Item Dry Eye Questionnaire scores to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Measure of the volume of tears in mm using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Blink Rate to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Manual subjective count of the number of blinks using the Oculus Keratograph 5M instrument.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Dry Eye Disease and Meibomian Gland Dysfunction</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>The number of participants diagnosed with dry eye disease and Meibomian gland dysfunction according to established clinical diagnostic criteria (Wolffsohn et al, 2017 ; Tomlinson et al, 2011).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Total Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Measure of total corneal nerve length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Blood Flow to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Measure of blood flow using laser doppler flowmetry instrument.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Tear Constituent to the Final Follow-up 3 Months After Final Treatment Session</measure>
      <time_frame>Baseline up to 3 months after final treatment session</time_frame>
      <description>Measure of tear constituent using Schirmer strip tear sampling technique.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Dry Eye Syndromes</condition>
    <condition>Meibomian Gland Dysfunction</condition>
    <arm_group>
      <arm_group_label>Actual IPL and LLLT</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>IPL and LLLT 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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham IPL and LLLT</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Sham IPL will be administered by placing a separate empty IPL cartridge on the lower eyelid regions of the patient's other eye while a working IPL cartridge (Espansione Group Ltd Eye-light unit) simulates a light pulse pointed away from the patient's face, after entering the Pult meiboscore and Fitzpatrick skin grading into the unit. Five simulated pulses will be administered. LLLT consisting of a wearable facial mask with red LEDs is then administered for 15 minutes.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Actual IPL</intervention_name>
      <description>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</description>
      <arm_group_label>Actual IPL and LLLT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sham IPL</intervention_name>
      <description>Simulated five light pulses along lower lid region of the other eye of the same participant</description>
      <arm_group_label>Sham IPL and LLLT</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>LLLT</intervention_name>
      <description>Mask with LEDs transferring a total of about 32 J/cm^2 of energy to facial and eyelids region with their eyes closed</description>
      <arm_group_label>Actual IPL and LLLT</arm_group_label>
      <arm_group_label>Sham IPL and LLLT</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Individuals with dry eye disease symptoms (Ocular Surface Disease Index questionnaire&#xD;
               (OSDI) score ≥ 13 or Dry Eye Questionnaire (DEQ5) score &gt; 6) and signs (tear film&#xD;
               instability measured with non-invasive tear break-up time &lt; 10 s or ocular surface&#xD;
               damage measured using special dyes placed on the front surface of the eyes that&#xD;
               temporarily stains any aggravated or damaged cells: &gt; 5 corneal spots, &gt; 9&#xD;
               conjunctival spots or lid margin staining ≥ 2mm in length and ≥ 25% in width)&#xD;
               (Wolffsohn et al., 2017)&#xD;
  &#xD;
            -  Individuals need to also have Meibomian gland dysfunction. The diagnosis of Meibomian&#xD;
               gland dysfunction depends on how many of 5 glands in the central lower eyelid can&#xD;
               express oil, and the quality of the oil. A diagnosis is made if there is decreased&#xD;
               expressibility (grade 1-3 on the Pflugfelder scale) and reduced quality of oil (grade&#xD;
               1-3 on Bron scale). Any presence of gland blockage and/or loss of oil glands grade 2&#xD;
               to grade 4 of either eyelid [Pult and Reide-Pult, 2013]) will also justify a diagnosis&#xD;
               of Meibomian gland dysfunction&#xD;
  &#xD;
            -  Age ≥ 18 years, male or female&#xD;
  &#xD;
            -  Able to provide written consent in English&#xD;
  &#xD;
            -  Able to attend multiple visits (4 treatment visits) and followed up for 2 weeks and 3&#xD;
               months after final treatment&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Contraindications to IPL treatment (Individuals with darker skin types - Fitzpatrick&#xD;
               skin type V or VI, photosensitive epilepsy, tattoos, implants, electrical or acoustic&#xD;
               prosthetics, semi-permanent make-up, pigmented lesions or skin cancer in the treatment&#xD;
               area, pacemakers, use of photosensitising medication the past 3 months or during&#xD;
               treatment period)&#xD;
  &#xD;
            -  Facial or ocular IPL or LLLT treatment within the past 6 months or during study period&#xD;
               in addition to those provided in the study&#xD;
  &#xD;
            -  Use of topical medical eyedrops in the past 3 months or during study period&#xD;
  &#xD;
            -  Contact lens wear in the past 2 weeks or during study period&#xD;
  &#xD;
            -  Systemic conditions that can cause dry eye disease or corneal nerve loss including&#xD;
               diabetes and Sjögren's syndrome&#xD;
  &#xD;
            -  Other active ocular surface diseases or history of ocular surgery or corneal&#xD;
               infections&#xD;
  &#xD;
            -  Individuals with 1 eye&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>James S Wolffsohn, PhD</last_name>
      <role>Study Director</role>
      <affiliation>Aston University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jeremy Chung Bo Chiang, PhD</last_name>
      <phone>+441212043934</phone>
      <phone_ext>3934</phone_ext>
      <email>j.chiang@aston.ac.uk</email>
    </overall_contact>
    <reference>
      <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.</citation>
      <PMID>21450918</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>23108007</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>28736342</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>10815152</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>20093066</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>27345733</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Aston University</investigator_affiliation>
      <investigator_full_name>Jeremy Chiang</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Intense pulsed light therapy</keyword>
    <keyword>Low-level light therapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dry Eye Syndromes</mesh_term>
      <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
      <mesh_term>Eye Diseases</mesh_term>
      <mesh_term>Meibomian Gland Dysfunction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The investigators are planning to deposit deidentified datasets in a publicly and freely available data repository site.</ipd_description>
      <ipd_time_frame>Data will be available at the end of the study before publication of the findings in a peer-reviewed journal.</ipd_time_frame>
      <ipd_access_criteria>The dataset will be publicly and freely available.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06004895
  org study id: HLS21118
  nct id: NCT06004895
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  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.
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Change from Baseline in Non-invasive Tear Break Up Time to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline and 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Ocular Surface Disease Index scores to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in 5-Item Dry Eye Questionnaire scores to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in Tear Meniscus Height to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Measure of the volume of tears in mm using the Oculus Keratograph 5M instrument. An average of 3 measurements is obtained.
  measure: Change from Baseline in Lipid Layer Pattern Grading to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Bulbar Conjunctival Hyperaemia to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Blink Rate to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Manual subjective count of the number of blinks using the Oculus Keratograph 5M instrument.
  measure: Change from Baseline in Visual Acuity to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Fluorescein Corneal Staining to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Lissamine Green Bulbar Conjunctival Staining to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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.
  measure: Change from Baseline in Lissamine Green Lid Wiper Epitheliopathy to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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
  measure: Change from Baseline in Meibography Meiboscore to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in Demodex Presence to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in Number of Blocked or Capped Meibomian Glands to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Subjective assessment of the number of blocked or capped Meibomian Glands using slit lamp biomicroscopy and white light illumination.
  measure: Change from Baseline in Lid Margin Telangiectasia Grading to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in Meibum Expressibility to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Change from Baseline in Meibum Quality to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: 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).
  measure: Number of Participants with Dry Eye Disease and Meibomian Gland Dysfunction
  time frame: Baseline up to 3 months after final treatment session
  description: The number of participants diagnosed with dry eye disease and Meibomian gland dysfunction according to established clinical diagnostic criteria (Wolffsohn et al, 2017 ; Tomlinson et al, 2011).
  measure: Change from Baseline in Total Corneal Nerve Length to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Measure of total corneal nerve length of sub-basal nerve plexi images obtained from in-vivo corneal confocal microscopy.
  measure: Change from Baseline in Blood Flow to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Measure of blood flow using laser doppler flowmetry instrument.
  measure: Change from Baseline in Tear Constituent to the Final Follow-up 3 Months After Final Treatment Session
  time frame: Baseline up to 3 months after final treatment session
  description: Measure of tear constituent using Schirmer strip tear sampling technique.
  arm group label: Actual IPL and LLLT
  arm group type: Experimental
  description: IPL and LLLT 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.
  arm group label: Sham IPL and LLLT
  arm group type: Sham Comparator
  description: Sham IPL will be administered by placing a separate empty IPL cartridge on the lower eyelid regions of the patient's other eye while a working IPL cartridge (Espansione Group Ltd Eye-light unit) simulates a light pulse pointed away from the patient's face, after entering the Pult meiboscore and Fitzpatrick skin grading into the unit. Five simulated pulses will be administered. LLLT consisting of a wearable facial mask with red LEDs is then administered for 15 minutes.
  intervention type: Device
  intervention name: Actual IPL
  description: 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
  arm group label: Actual IPL and LLLT
  intervention type: Device
  intervention name: Sham IPL
  description: Simulated five light pulses along lower lid region of the other eye of the same participant
  arm group label: Sham IPL and LLLT
  intervention type: Device
  intervention name: LLLT
  description: Mask with LEDs transferring a total of about 32 J/cm^2 of energy to facial and eyelids region with their eyes closed
  arm group label: Actual IPL and LLLT
  arm group label: Sham IPL and LLLT
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: James S Wolffsohn, PhD
  role: Study Director
  affiliation: Aston University
  last name: Jeremy Chung Bo Chiang, PhD
  phone: +441212043934
  phone ext: 3934
  email: j.chiang@aston.ac.uk
  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.
  PMID: 21450918
  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.
  PMID: 23108007
  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.
  PMID: 28736342
  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.
  PMID: 10815152
  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.
  PMID: 20093066
  citation: 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
  responsible party type: Principal Investigator
  investigator affiliation: Aston University
  investigator full name: Jeremy Chiang
  investigator title: Principal Investigator
  mesh term: Dry Eye Syndromes
  mesh term: Keratoconjunctivitis Sicca
  mesh term: Eye Diseases
  mesh term: Meibomian Gland Dysfunction
  sharing ipd: Yes
  ipd description: The investigators are planning to deposit deidentified datasets in a publicly and freely available data repository site.
  ipd time frame: Data will be available at the end of the study before publication of the findings in a peer-reviewed journal.
  ipd access criteria: The dataset will be publicly and freely available.