<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/NCT03767530</url>
  </required_header>
  <id_info>
    <org_study_id>OF18-00006</org_study_id>
    <nct_id>NCT03767530</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Thermic Devices in the Treatment of Meibomian Gland Dysfunction</brief_title>
  <official_title>Efficacy and Safety of Thermic Devices in the Treatment of Meibomian Gland Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad Autonoma de Nuevo Leon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Universitario Dr. Jose E. Gonzalez</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad Autonoma de Nuevo Leon</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 syndrome is a common eye disease that affects 1 to 2 out of 10 persons around the&#xD;
      planet. One common cause of this disease is the meibomian gland dysfunction. Meibomian glands&#xD;
      are very small glands located at the rim of the eyelids that produce an oily substance that&#xD;
      prevents the evaporation of tears. When these glands are compromised, the tear film&#xD;
      evaporates quickly and the eyes dry up. This disease presents as eye irritation, foreign body&#xD;
      sensation, inflammation, etc. The treatment of choice for MGD is eyelid massage and warm&#xD;
      compresses 2 times a day. However, these treatments not always work perfectly, and as a&#xD;
      result, patients find it hard to follow doctor's orders. Another kind of treatment is thermal&#xD;
      therapy. There are several devices that are designed to apply heat on the eyelids, such as&#xD;
      Lipiflow, MiBo Thermoflo, and Blephasteam. In this study, we want to find out whether thermal&#xD;
      therapy with MiBo Thermoflo works better than warm compresses and eyelid massage use in the&#xD;
      treatment of dry eye caused by MGD. To do this, we will select several patients and will&#xD;
      assign them randomly to either the group with thermal therapy with MiBo Thermoflo or to the&#xD;
      group with warm compresses and eyelid massage. The Mibo group will receive 3 sessions of&#xD;
      thermal therapy at 2 weeks interval and the control group warm compresses and eyelid massage&#xD;
      2 times per day. All subjects will have a follow up of 24 weeks and we will compare results&#xD;
      for both groups at the end of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dry eye syndrome is considered one of the most important ophthalmologic diseases, affecting&#xD;
      10 to 20% of the general population. Of these, 3.7% to 70% of cases are due to meibomian&#xD;
      gland dysfunction (MGD). MGD is a chronic diffuse disease characterized by terminal duct&#xD;
      obstruction and/or qualitative/quantitative changes in gland secretion. This causes a&#xD;
      disruption in the tear film, ocular irritation symptom, inflammation, and ocular surface&#xD;
      symptoms. The gold standard for the treatment of meibomian dysfunction is the use of warm&#xD;
      compresses and eyelid massage 2 times a day. These have variable results and consequently&#xD;
      patient's adherence to treatment is low. An alternative treatment is the use of thermal&#xD;
      therapy devices such as Lipiflow, MiBo Thermoflo, and Blephasteam. The objective of this&#xD;
      study is to determine if the thermal device MiBo Thermoflo is more effective than warm&#xD;
      compresses and eyelid massage in the treatment of dry eye secondary to MGD. Participants will&#xD;
      be randomly assigned to one of two groups: the Mibo group will receive 3 sessions of thermal&#xD;
      therapy at 2 weeks interval and the control group warm compresses and eyelid massage 2 times&#xD;
      per day. All subjects will have follow up of 24 weeks and we will compare results for both&#xD;
      groups at the end of the study. During the protocol patients in both groups will continue&#xD;
      with their standard treatment for dry eye as needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">September 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>All subjects will be ophthalmologically evaluated before treatment and at weeks 8, 16 and 24. Subjects will be randomly assigned into 2 study groups. Mibo group will have 3 sessions (basal, week 2, week 4) of thermal therapy with Mibo Thermoflo in both eyes. The control group will use warm compresses and eyelid massage 2 times per day in both eyes. At the week 16 control group will also have 3 sessions of Mibo therapy at 2 weeks interval.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Not blinded study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Meibomian gland expressibility</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Changes in meibomian gland structure will be evaluated by meibomian gland expressibility.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Meibum quality</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Changes in meibomian gland structure will be evaluated with the meibum quality in slit lamp graded as: clear, opaque, granular and toothpaste for meibum worst secretion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Corneal and conjunctival staining with fluorescein dye</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Corneal and conjunctival staining with lissamine green dye</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tear Break-up Time (TBUT)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Tear stability will be measured with Tear Break-up Time (TBUT). A result &gt;10 seconds will be considered normal, a result &lt;10 seconds will be considered pathological.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Schirmer test with and without anesthesia</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Tear production will be measured by Schirmer test with and without anesthesia. A Schirmer test &gt;10 mm will be considered normal, a result &gt;5 mm pathological. The Schirmer test with anesthesia &gt;15 mm is consider normal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Symptom Assessment in Dry Eye questionnaire (SANDE)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE) questionnaire. The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ocular Surface Disease Index (OSDI)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients are asked to rate their responses on a 0 to 4 scale where 0 represents &quot;none of the time&quot;, 1 &quot;some of the time&quot;, 2 &quot;half of the time&quot;, 3 &quot;most of the time&quot;, and 4 &quot;all of the time&quot;. The total score is calculated using the following formula: ([sum of scores for all questions answered x 100] / [total number of questions answered x 4]). Lower scores represent a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dry Eye Questionnaire 5 (DEQ-5)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tear osmolarity</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Patients with dry eye have increased levels of tear osmolarity wich is one of tear inflammation biomarkers. Tear osmolarity will be performed with Tear Lab Osmolarity System, a result of 308 mOsm/L or higher indicates dry eye disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in tear of matrix metalloproteinase 9 (MMP-9)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>MMP-9 is an inflammatory biomarker wich is elevated in the tears of patients with dry eye and an early diagnostic evaluation, it is realized in consulting room with the InflammaDry test (Rapid Pathogen Screening Inc.). The presence of 1 line is a negative result and two lines means positive result.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Non-Invasive Keratograph Break-up Time (NIKBUT)</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>NIKBUT will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tear meniscus height</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Tear meniscus height will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Conjuctival hyperemia</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Conjuctival hypermeia will be graded with JENVIS Scale performed by Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. Conjuctival hyperemia will be . graded as: none, mild moderate or severe.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid layer thickness</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Lipid layer thickness will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Basal to 24 weeks</time_frame>
    <description>Adverse events will be evaluated during the ophthalmic evaluation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short term changes with corneal and conjunctival staining with fluorescein dye</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term changes with corneal and conjunctival staining with lissamine green dye</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term changes in tear stability</measure>
    <time_frame>These parameterd will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in tear stability will be measured with Tear Break-up Time (TBUT). A result &gt;10 seconds will be considered normal, a result &lt;10 seconds will be considered pathological.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term changes in Symptom Assessment in Dry Eye questionnaire (SANDE)</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE). The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms. A less rate prove changes in ocular surface symptoms and quality of life improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term changes in Ocular Surface Disease Index (OSDI)</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers.. A less rate prove changes in ocular surface symptoms and quality of life improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term changes in Dry Eye Questionnaire 5 (DEQ-5)</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Short term changes in ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level. A less rate prove changes in coular surface symptoms and quality of life improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eyelid skin temperature</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Eyelid skin temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corneal conjunctival temperature</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Corneal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bulbar conjunctival temperature</measure>
    <time_frame>These parameters will be evaluated before sessions of termal therapy at week 2 and week 4</time_frame>
    <description>Bulbar conjunctival temperature will be measured with the thermographic infrrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tarsal conjunctival temperature</measure>
    <time_frame>These parameters will be evaluated before sessions of thermal therapy at week 2 and week 4.</time_frame>
    <description>Tarsal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Meibomian Gland Dysfunction</condition>
  <arm_group>
    <arm_group_label>Mibo Thermoflo (thermal device)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 sessions at 2 weeks interval (basal, week 2, week 4)of 11 minutes per eye of thermal therapy with Mibo Thermoflo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Warm compresses and eyelid massage</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 times per day, 11 minutes per eye.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mibo Thermoflo</intervention_name>
    <description>Thermal therapy with Mibo Thermoflo for 11 minutes per eye, during each session.</description>
    <arm_group_label>Mibo Thermoflo (thermal device)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Warm compresses and eyelid massage</intervention_name>
    <description>Warm compresses plus eyelid massage 2 times per day 11 minutes per eye.</description>
    <arm_group_label>Warm compresses and eyelid massage</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with:&#xD;
&#xD;
               -  Dry eye syndrome with meibomian gland dysfunction alone or in combination of&#xD;
                  other type of dry eye.&#xD;
&#xD;
               -  Patients who were previously treated with eyelid massages and warm compresses&#xD;
                  without any improvement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women.&#xD;
&#xD;
          -  History of ocular surgery within three months prior to inclusion.&#xD;
&#xD;
          -  History of trauma, infection or inflammation within three months prior to inclusion.&#xD;
&#xD;
          -  Contact lens use in the last week before inclusion.&#xD;
&#xD;
          -  Patients with active ocular allergic disease.&#xD;
&#xD;
          -  Patient with microbial keratitis.&#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>Karim Mohamed-Noriega, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Karim Mohamed-Noriega, M.D.</last_name>
    <phone>+52 8183469259</phone>
    <email>karim.mohamednrg@uanl.edu.mx,drkmohamed1@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Departamento de Oftalmologia, Hospital Universitario &quot;Dr. Jose Eleuterio Gonzalez&quot;</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo Leon</state>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karim Mohamed-Noriega, M.D.</last_name>
      <phone>+52 81 83469259</phone>
      <email>karim.mohamednrg@uanl.edu.mx, drkmohamed1@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Karim Mohamed-Noriega, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>Arita R, Morishige N, Shirakawa R, Sato Y, Amano S. Effects of Eyelid Warming Devices on Tear Film Parameters in Normal Subjects and Patients with Meibomian Gland Dysfunction. Ocul Surf. 2015 Oct;13(4):321-30. doi: 10.1016/j.jtos.2015.04.005. Epub 2015 May 30.</citation>
    <PMID>26031204</PMID>
  </reference>
  <reference>
    <citation>Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20.</citation>
    <PMID>28736335</PMID>
  </reference>
  <reference>
    <citation>Foulks, G. N., Lemp, M., Jester, J., Sutphin, J., Murube, J., &amp; Novack, G. (2007). report of the international dry eye workshop (DEWS). Ocul Surf, 5(2), 65-204. Foulks, G. N., Lemp, M., Jester, J., Sutphin, J., Murube, J., &amp; Novack, G. (2007). Report of the international dry eye workshop (DEWS). Ocul Surf, 5(2), 65-204.</citation>
  </reference>
  <reference>
    <citation>Geerling G, Tauber J, Baudouin C, Goto E, Matsumoto Y, O'Brien T, Rolando M, Tsubota K, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2050-64. doi: 10.1167/iovs.10-6997g. No abstract available.</citation>
    <PMID>21450919</PMID>
  </reference>
  <reference>
    <citation>Hom M, De Land P. Prevalence and severity of symptomatic dry eyes in Hispanics. Optom Vis Sci. 2005 Mar;82(3):206-8. doi: 10.1097/01.opx.0000156310.45736.fa.</citation>
    <PMID>15767875</PMID>
  </reference>
  <reference>
    <citation>Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res. 2004 Jul;23(4):449-74. doi: 10.1016/j.preteyeres.2004.04.003.</citation>
    <PMID>15219877</PMID>
  </reference>
  <reference>
    <citation>Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017 Jul;15(3):575-628. doi: 10.1016/j.jtos.2017.05.006. Epub 2017 Jul 20.</citation>
    <PMID>28736343</PMID>
  </reference>
  <reference>
    <citation>Kenrick CJ, Alloo SS. The Limitation of Applying Heat to the External Lid Surface: A Case of Recalcitrant Meibomian Gland Dysfunction. Case Rep Ophthalmol. 2017 Jan 16;8(1):7-12. doi: 10.1159/000455087. eCollection 2017 Jan-Apr.</citation>
    <PMID>28203190</PMID>
  </reference>
  <reference>
    <citation>Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012 May;31(5):472-8. doi: 10.1097/ICO.0b013e318225415a.</citation>
    <PMID>22378109</PMID>
  </reference>
  <reference>
    <citation>Mori A, Shimazaki J, Shimmura S, Fujishima H, Oguchi Y, Tsubota K. Disposable eyelid-warming device for the treatment of meibomian gland dysfunction. Jpn J Ophthalmol. 2003 Nov-Dec;47(6):578-86. doi: 10.1016/s0021-5155(03)00142-4.</citation>
    <PMID>14636848</PMID>
  </reference>
  <reference>
    <citation>Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, Foulks GN. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7. doi: 10.1167/iovs.10-6997b. Print 2011 Mar. No abstract available.</citation>
    <PMID>21450914</PMID>
  </reference>
  <reference>
    <citation>Pult H, Riede-Pult BH, Purslow C. A comparison of an eyelid-warming device to traditional compress therapy. Optom Vis Sci. 2012 Jul;89(7):E1035-41. doi: 10.1097/OPX.0b013e31825c3479.</citation>
    <PMID>22729167</PMID>
  </reference>
  <reference>
    <citation>Qiao J, Yan X. Emerging treatment options for meibomian gland dysfunction. Clin Ophthalmol. 2013;7:1797-803. doi: 10.2147/OPTH.S33182. Epub 2013 Sep 9.</citation>
    <PMID>24043929</PMID>
  </reference>
  <reference>
    <citation>Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. doi: 10.1167/iovs.10-6997e. Print 2011 Mar. No abstract available.</citation>
    <PMID>21450917</PMID>
  </reference>
  <reference>
    <citation>Wang MT, Jaitley Z, Lord SM, Craig JP. Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction. Optom Vis Sci. 2015 Sep;92(9):e321-6. doi: 10.1097/OPX.0000000000000601.</citation>
    <PMID>25955642</PMID>
  </reference>
  <reference>
    <citation>Wang X, Lu X, Yang J, Wei R, Yang L, Zhao S, Wang X. Evaluation of Dry Eye and Meibomian Gland Dysfunction in Teenagers with Myopia through Noninvasive Keratograph. J Ophthalmol. 2016;2016:6761206. doi: 10.1155/2016/6761206. Epub 2016 Jan 6.</citation>
    <PMID>26881059</PMID>
  </reference>
  <reference>
    <citation>Stetson G. &amp; Kenrick Ch. (2018). A comparision of four warm compress devices. The Association of Research in Vision and Ophthalmology (ARVO). Honolulu Hawaii. 953-B0131.</citation>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad Autonoma de Nuevo Leon</investigator_affiliation>
    <investigator_full_name>Karim Mohamed-Noriega</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Meibomian gland dysfunction</keyword>
  <keyword>Mibo</keyword>
  <keyword>MGD</keyword>
  <keyword>Dry eye disease</keyword>
  <keyword>Thermic devices</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meibomian Gland Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03767530
org study id: OF18-00006
nct id: NCT03767530
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Dry eye syndrome is a common eye disease that affects 1 to 2 out of 10 persons around the
      planet. One common cause of this disease is the meibomian gland dysfunction. Meibomian glands
      are very small glands located at the rim of the eyelids that produce an oily substance that
      prevents the evaporation of tears. When these glands are compromised, the tear film
      evaporates quickly and the eyes dry up. This disease presents as eye irritation, foreign body
      sensation, inflammation, etc. The treatment of choice for MGD is eyelid massage and warm
      compresses 2 times a day. However, these treatments not always work perfectly, and as a
      result, patients find it hard to follow doctor's orders. Another kind of treatment is thermal
      therapy. There are several devices that are designed to apply heat on the eyelids, such as
      Lipiflow, MiBo Thermoflo, and Blephasteam. In this study, we want to find out whether thermal
      therapy with MiBo Thermoflo works better than warm compresses and eyelid massage use in the
      treatment of dry eye caused by MGD. To do this, we will select several patients and will
      assign them randomly to either the group with thermal therapy with MiBo Thermoflo or to the
      group with warm compresses and eyelid massage. The Mibo group will receive 3 sessions of
      thermal therapy at 2 weeks interval and the control group warm compresses and eyelid massage
      2 times per day. All subjects will have a follow up of 24 weeks and we will compare results
      for both groups at the end of the study.
Dry eye syndrome is considered one of the most important ophthalmologic diseases, affecting
      10 to 20% of the general population. Of these, 3.7% to 70% of cases are due to meibomian
      gland dysfunction (MGD). MGD is a chronic diffuse disease characterized by terminal duct
      obstruction and/or qualitative/quantitative changes in gland secretion. This causes a
      disruption in the tear film, ocular irritation symptom, inflammation, and ocular surface
      symptoms. The gold standard for the treatment of meibomian dysfunction is the use of warm
      compresses and eyelid massage 2 times a day. These have variable results and consequently
      patient's adherence to treatment is low. An alternative treatment is the use of thermal
      therapy devices such as Lipiflow, MiBo Thermoflo, and Blephasteam. The objective of this
      study is to determine if the thermal device MiBo Thermoflo is more effective than warm
      compresses and eyelid massage in the treatment of dry eye secondary to MGD. Participants will
      be randomly assigned to one of two groups: the Mibo group will receive 3 sessions of thermal
      therapy at 2 weeks interval and the control group warm compresses and eyelid massage 2 times
      per day. All subjects will have follow up of 24 weeks and we will compare results for both
      groups at the end of the study. During the protocol patients in both groups will continue
      with their standard treatment for dry eye as needed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All subjects will be ophthalmologically evaluated before treatment and at weeks 8, 16 and 24. Subjects will be randomly assigned into 2 study groups. Mibo group will have 3 sessions (basal, week 2, week 4) of thermal therapy with Mibo Thermoflo in both eyes. The control group will use warm compresses and eyelid massage 2 times per day in both eyes. At the week 16 control group will also have 3 sessions of Mibo therapy at 2 weeks interval.
primary purpose: Treatment
masking: None (Open Label)
masking description: Not blinded study.
measure: Meibomian gland expressibility
time frame: Basal to 24 weeks
description: Changes in meibomian gland structure will be evaluated by meibomian gland expressibility.
measure: Meibum quality
time frame: Basal to 24 weeks
description: Changes in meibomian gland structure will be evaluated with the meibum quality in slit lamp graded as: clear, opaque, granular and toothpaste for meibum worst secretion.
measure: Corneal and conjunctival staining with fluorescein dye
time frame: Basal to 24 weeks
description: Ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye.
measure: Corneal and conjunctival staining with lissamine green dye
time frame: Basal to 24 weeks
description: Ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye.
measure: Tear Break-up Time (TBUT)
time frame: Basal to 24 weeks
description: Tear stability will be measured with Tear Break-up Time (TBUT). A result >10 seconds will be considered normal, a result <10 seconds will be considered pathological.
measure: Schirmer test with and without anesthesia
time frame: Basal to 24 weeks
description: Tear production will be measured by Schirmer test with and without anesthesia. A Schirmer test >10 mm will be considered normal, a result >5 mm pathological. The Schirmer test with anesthesia >15 mm is consider normal.
measure: Symptom Assessment in Dry Eye questionnaire (SANDE)
time frame: Basal to 24 weeks
description: Ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE) questionnaire. The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms.
measure: Ocular Surface Disease Index (OSDI)
time frame: Basal to 24 weeks
description: Ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients are asked to rate their responses on a 0 to 4 scale where 0 represents "none of the time", 1 "some of the time", 2 "half of the time", 3 "most of the time", and 4 "all of the time". The total score is calculated using the following formula: ([sum of scores for all questions answered x 100] / [total number of questions answered x 4]). Lower scores represent a better outcome.
measure: Dry Eye Questionnaire 5 (DEQ-5)
time frame: Basal to 24 weeks
description: Ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level.
measure: Tear osmolarity
time frame: Basal to 24 weeks
description: Patients with dry eye have increased levels of tear osmolarity wich is one of tear inflammation biomarkers. Tear osmolarity will be performed with Tear Lab Osmolarity System, a result of 308 mOsm/L or higher indicates dry eye disease.
measure: Change in tear of matrix metalloproteinase 9 (MMP-9)
time frame: Basal to 24 weeks
description: MMP-9 is an inflammatory biomarker wich is elevated in the tears of patients with dry eye and an early diagnostic evaluation, it is realized in consulting room with the InflammaDry test (Rapid Pathogen Screening Inc.). The presence of 1 line is a negative result and two lines means positive result.
measure: Non-Invasive Keratograph Break-up Time (NIKBUT)
time frame: Basal to 24 weeks
description: NIKBUT will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.
measure: Tear meniscus height
time frame: Basal to 24 weeks
description: Tear meniscus height will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.
measure: Conjuctival hyperemia
time frame: Basal to 24 weeks
description: Conjuctival hypermeia will be graded with JENVIS Scale performed by Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings. Conjuctival hyperemia will be . graded as: none, mild moderate or severe.
measure: Lipid layer thickness
time frame: Basal to 24 weeks
description: Lipid layer thickness will be measured with Keratograph 5M. A JENVIS Dry Eye report will be generated to document findings.
measure: Adverse events
time frame: Basal to 24 weeks
description: Adverse events will be evaluated during the ophthalmic evaluation.
measure: Short term changes with corneal and conjunctival staining with fluorescein dye
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with fluorescein dye.
measure: Short term changes with corneal and conjunctival staining with lissamine green dye
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in ocular surface damage will be graded with corneal and conjunctival staining with lissamine green dye.
measure: Short term changes in tear stability
time frame: These parameterd will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in tear stability will be measured with Tear Break-up Time (TBUT). A result >10 seconds will be considered normal, a result <10 seconds will be considered pathological.
measure: Short term changes in Symptom Assessment in Dry Eye questionnaire (SANDE)
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in ocular surface symptoms will be assessed by the Symptom Assessment in Dry Eye (SANDE). The SANDE questionnaire has two questions presented in a visual scale. The two questions assess the frequency and severity of dry eye symptoms. A less rate prove changes in ocular surface symptoms and quality of life improvement.
measure: Short term changes in Ocular Surface Disease Index (OSDI)
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers.. A less rate prove changes in ocular surface symptoms and quality of life improvement.
measure: Short term changes in Dry Eye Questionnaire 5 (DEQ-5)
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Short term changes in ocular surface symptoms will be assessed by the Dry Eye Questionnaire 5 (DEQ-5). The Dry Eye Questionnaire 5 asses habitual dry eye symptoms (discomfort, dryness and wetty eyes) and severity level. A less rate prove changes in coular surface symptoms and quality of life improvement.
measure: Eyelid skin temperature
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Eyelid skin temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.
measure: Corneal conjunctival temperature
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Corneal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.
measure: Bulbar conjunctival temperature
time frame: These parameters will be evaluated before sessions of termal therapy at week 2 and week 4
description: Bulbar conjunctival temperature will be measured with the thermographic infrrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.
measure: Tarsal conjunctival temperature
time frame: These parameters will be evaluated before sessions of thermal therapy at week 2 and week 4.
description: Tarsal conjunctival temperature will be measured with the thermographic infrared scientific equipment FLIR SC4000 to verify if 42 celsius degree are obtain as maker recommends.
arm group label: Mibo Thermoflo (thermal device)
arm group type: Experimental
description: 3 sessions at 2 weeks interval (basal, week 2, week 4)of 11 minutes per eye of thermal therapy with Mibo Thermoflo.
arm group label: Warm compresses and eyelid massage
arm group type: Active Comparator
description: 2 times per day, 11 minutes per eye.
intervention type: Device
intervention name: Mibo Thermoflo
description: Thermal therapy with Mibo Thermoflo for 11 minutes per eye, during each session.
arm group label: Mibo Thermoflo (thermal device)
intervention type: Other
intervention name: Warm compresses and eyelid massage
description: Warm compresses plus eyelid massage 2 times per day 11 minutes per eye.
arm group label: Warm compresses and eyelid massage
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karim Mohamed-Noriega, M.D.
role: Principal Investigator
affiliation: Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez
last name: Karim Mohamed-Noriega, M.D.
phone: +52 8183469259
email: karim.mohamednrg@uanl.edu.mx,drkmohamed1@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Mexico
citation: Arita R, Morishige N, Shirakawa R, Sato Y, Amano S. Effects of Eyelid Warming Devices on Tear Film Parameters in Normal Subjects and Patients with Meibomian Gland Dysfunction. Ocul Surf. 2015 Oct;13(4):321-30. doi: 10.1016/j.jtos.2015.04.005. Epub 2015 May 30.
PMID: 26031204
citation: Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20.
PMID: 28736335
citation: Foulks, G. N., Lemp, M., Jester, J., Sutphin, J., Murube, J., & Novack, G. (2007). report of the international dry eye workshop (DEWS). Ocul Surf, 5(2), 65-204. Foulks, G. N., Lemp, M., Jester, J., Sutphin, J., Murube, J., & Novack, G. (2007). Report of the international dry eye workshop (DEWS). Ocul Surf, 5(2), 65-204.
citation: Geerling G, Tauber J, Baudouin C, Goto E, Matsumoto Y, O'Brien T, Rolando M, Tsubota K, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2050-64. doi: 10.1167/iovs.10-6997g. No abstract available.
PMID: 21450919
citation: Hom M, De Land P. Prevalence and severity of symptomatic dry eyes in Hispanics. Optom Vis Sci. 2005 Mar;82(3):206-8. doi: 10.1097/01.opx.0000156310.45736.fa.
PMID: 15767875
citation: Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res. 2004 Jul;23(4):449-74. doi: 10.1016/j.preteyeres.2004.04.003.
PMID: 15219877
citation: Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017 Jul;15(3):575-628. doi: 10.1016/j.jtos.2017.05.006. Epub 2017 Jul 20.
PMID: 28736343
citation: Kenrick CJ, Alloo SS. The Limitation of Applying Heat to the External Lid Surface: A Case of Recalcitrant Meibomian Gland Dysfunction. Case Rep Ophthalmol. 2017 Jan 16;8(1):7-12. doi: 10.1159/000455087. eCollection 2017 Jan-Apr.
PMID: 28203190
citation: Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012 May;31(5):472-8. doi: 10.1097/ICO.0b013e318225415a.
PMID: 22378109
citation: Mori A, Shimazaki J, Shimmura S, Fujishima H, Oguchi Y, Tsubota K. Disposable eyelid-warming device for the treatment of meibomian gland dysfunction. Jpn J Ophthalmol. 2003 Nov-Dec;47(6):578-86. doi: 10.1016/s0021-5155(03)00142-4.
PMID: 14636848
citation: Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Den S, Foulks GN. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7. doi: 10.1167/iovs.10-6997b. Print 2011 Mar. No abstract available.
PMID: 21450914
citation: Pult H, Riede-Pult BH, Purslow C. A comparison of an eyelid-warming device to traditional compress therapy. Optom Vis Sci. 2012 Jul;89(7):E1035-41. doi: 10.1097/OPX.0b013e31825c3479.
PMID: 22729167
citation: Qiao J, Yan X. Emerging treatment options for meibomian gland dysfunction. Clin Ophthalmol. 2013;7:1797-803. doi: 10.2147/OPTH.S33182. Epub 2013 Sep 9.
PMID: 24043929
citation: Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. doi: 10.1167/iovs.10-6997e. Print 2011 Mar. No abstract available.
PMID: 21450917
citation: Wang MT, Jaitley Z, Lord SM, Craig JP. Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction. Optom Vis Sci. 2015 Sep;92(9):e321-6. doi: 10.1097/OPX.0000000000000601.
PMID: 25955642
citation: Wang X, Lu X, Yang J, Wei R, Yang L, Zhao S, Wang X. Evaluation of Dry Eye and Meibomian Gland Dysfunction in Teenagers with Myopia through Noninvasive Keratograph. J Ophthalmol. 2016;2016:6761206. doi: 10.1155/2016/6761206. Epub 2016 Jan 6.
PMID: 26881059
citation: Stetson G. & Kenrick Ch. (2018). A comparision of four warm compress devices. The Association of Research in Vision and Ophthalmology (ARVO). Honolulu Hawaii. 953-B0131.
responsible party type: Principal Investigator
investigator affiliation: Universidad Autonoma de Nuevo Leon
investigator full name: Karim Mohamed-Noriega
investigator title: Professor
mesh term: Meibomian Gland Dysfunction
sharing ipd: No