<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/NCT03230981</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000867</org_study_id>
    <nct_id>NCT03230981</nct_id>
  </id_info>
  <brief_title>Age-dependency of Cornea Biomechanics Using OCT Vibrography</brief_title>
  <official_title>Age-dependency of Cornea Biomechanics Measured by OCT Vibrography: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts Eye and Ear Infirmary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</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>
      The aim of this pilot study is to assess the ability of a new optical coherence tomography&#xD;
      system to obtain information on biomechanics of the cornea.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The cornea, the clear front window of the eye, consists of finely intertwined collagen&#xD;
      fibers, which give the cornea a microstructure that provides mechanical integrity necessary&#xD;
      to maintain its typical dome-shape against the intraocular pressure (IOP). Changes in the&#xD;
      biomechanical properties can lead to an abnormal corneal shape and refractive errors. As a&#xD;
      result, light is not perfectly focused onto the retina and the vision is affected. A typical&#xD;
      example of alterations in the cornea's biomechanical properties is found in patients with an&#xD;
      eye disorder called Keratoconus, which leads to progressive thinning of the cornea. Numerous&#xD;
      studies have shown that promising interventions like collagen crosslinking (CXL) can slow&#xD;
      down an arrest progression of ectatic eye diseases. Keratoconus, as a typical example,&#xD;
      although it cannot be cured, could be at least halted by CXL. Therefore, early diagnosis of&#xD;
      ectasia is crucial for the patient. Current diagnostic methods of ectasia are based on&#xD;
      morphological rather than biomechanical analysis. The irregular patterns of the cornea can be&#xD;
      detected by pachymetry and topography before clinical signs occur, but these tests cannot&#xD;
      reliably differentiate truly weak or keratoconic corneas from atypical normal ones.&#xD;
&#xD;
      These are compelling needs for improved diagnostic methods. More recently, and triggered by&#xD;
      those unmet needs, an interest in the mechanical properties of the cornea has emerged.&#xD;
      Typical examples of mechanical properties are elastic modulus and corneal stiffness.&#xD;
&#xD;
      In this pilot study the investigators will test the ability of a new OCT Vibrography system&#xD;
      to determine cornea material parameters. More precisely, the investigators will study the&#xD;
      oscillation response in human corneas in-vivo using a stimulus mechanism used to induce&#xD;
      vibrations by touching the surface of the cornea. A localized vibration source paired&#xD;
      together with phase-sensitive OCT to measure the frequency response function of the human&#xD;
      cornea and to analyze the dependency of the frequency response function on age. Additionally&#xD;
      the investigators will use Brillouin Microscopy data for computer simulations to validate OCT&#xD;
      Vibrography results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Actual">January 1, 2023</completion_date>
  <primary_completion_date type="Actual">January 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of subjects to successfully complete OCT Vibrography without serious unanticipated adverse events related to application of the device.</measure>
    <time_frame>1 year</time_frame>
    <description>Frequency and severity of all treatment-related adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Validation of OCT Vibrography data by means of Brillouin microscopy measurements of the in-vivo cornea</measure>
    <time_frame>1 year</time_frame>
    <description>Use of Brillouin microscopy in-vivo data for computer simulations to validate OCT Vibrography results.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Cornea</condition>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optical imaging of the cornea in healthy subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Optical imaging of the cornea in healthy subjects</intervention_name>
    <description>OCT vibrography and Brillouin microscopy</description>
    <arm_group_label>Healthy subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects between the ages of 18 to 79 years&#xD;
&#xD;
          -  Healthy normal subjects with no significant eye disease and no significant refractive&#xD;
             errors&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Volunteers with implanted intraocular lenses&#xD;
&#xD;
          -  Volunteers with LASIK or any other eye surgery, and monocular volunteers&#xD;
&#xD;
          -  Volunteers with restricted mobility, who cannot stand up, walk or sit still on a chair&#xD;
             without a back&#xD;
&#xD;
          -  Subjects who do not or cannot understand the instructions for imaging&#xD;
&#xD;
          -  Subjects with diabetes, glaucoma family history&#xD;
&#xD;
          -  Subjects who are pregnant and/or breastfeeding.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seok-Hyun Yun, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.</citation>
    <PMID>12719068</PMID>
  </reference>
  <reference>
    <citation>de Sanctis U, Loiacono C, Richiardi L, Turco D, Mutani B, Grignolo FM. Sensitivity and specificity of posterior corneal elevation measured by Pentacam in discriminating keratoconus/subclinical keratoconus. Ophthalmology. 2008 Sep;115(9):1534-9. doi: 10.1016/j.ophtha.2008.02.020. Epub 2008 Apr 11.</citation>
    <PMID>18405974</PMID>
  </reference>
  <reference>
    <citation>Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004 Mar;111(3):440-6. doi: 10.1016/j.ophtha.2003.06.020.</citation>
    <PMID>15019316</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 16, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Seok Hyun Yun</investigator_full_name>
    <investigator_title>Professor of Dermatology</investigator_title>
  </responsible_party>
  <keyword>biomechanics</keyword>
  <keyword>cornea</keyword>
  <keyword>optical coherence tomography</keyword>
  <keyword>vibrography</keyword>
  <keyword>brillouin microscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Corneal Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 21, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT03230981/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03230981
org study id: 2017P000867
nct id: NCT03230981
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this pilot study is to assess the ability of a new optical coherence tomography
      system to obtain information on biomechanics of the cornea.
The cornea, the clear front window of the eye, consists of finely intertwined collagen
      fibers, which give the cornea a microstructure that provides mechanical integrity necessary
      to maintain its typical dome-shape against the intraocular pressure (IOP). Changes in the
      biomechanical properties can lead to an abnormal corneal shape and refractive errors. As a
      result, light is not perfectly focused onto the retina and the vision is affected. A typical
      example of alterations in the cornea's biomechanical properties is found in patients with an
      eye disorder called Keratoconus, which leads to progressive thinning of the cornea. Numerous
      studies have shown that promising interventions like collagen crosslinking (CXL) can slow
      down an arrest progression of ectatic eye diseases. Keratoconus, as a typical example,
      although it cannot be cured, could be at least halted by CXL. Therefore, early diagnosis of
      ectasia is crucial for the patient. Current diagnostic methods of ectasia are based on
      morphological rather than biomechanical analysis. The irregular patterns of the cornea can be
      detected by pachymetry and topography before clinical signs occur, but these tests cannot
      reliably differentiate truly weak or keratoconic corneas from atypical normal ones.

      These are compelling needs for improved diagnostic methods. More recently, and triggered by
      those unmet needs, an interest in the mechanical properties of the cornea has emerged.
      Typical examples of mechanical properties are elastic modulus and corneal stiffness.

      In this pilot study the investigators will test the ability of a new OCT Vibrography system
      to determine cornea material parameters. More precisely, the investigators will study the
      oscillation response in human corneas in-vivo using a stimulus mechanism used to induce
      vibrations by touching the surface of the cornea. A localized vibration source paired
      together with phase-sensitive OCT to measure the frequency response function of the human
      cornea and to analyze the dependency of the frequency response function on age. Additionally
      the investigators will use Brillouin Microscopy data for computer simulations to validate OCT
      Vibrography results.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Number of subjects to successfully complete OCT Vibrography without serious unanticipated adverse events related to application of the device.
time frame: 1 year
description: Frequency and severity of all treatment-related adverse events
measure: Validation of OCT Vibrography data by means of Brillouin microscopy measurements of the in-vivo cornea
time frame: 1 year
description: Use of Brillouin microscopy in-vivo data for computer simulations to validate OCT Vibrography results.
arm group label: Healthy subjects
arm group type: Experimental
description: Optical imaging of the cornea in healthy subjects
intervention type: Device
intervention name: Optical imaging of the cornea in healthy subjects
description: OCT vibrography and Brillouin microscopy
arm group label: Healthy subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Seok-Hyun Yun, PhD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
citation: Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.
PMID: 12719068
citation: de Sanctis U, Loiacono C, Richiardi L, Turco D, Mutani B, Grignolo FM. Sensitivity and specificity of posterior corneal elevation measured by Pentacam in discriminating keratoconus/subclinical keratoconus. Ophthalmology. 2008 Sep;115(9):1534-9. doi: 10.1016/j.ophtha.2008.02.020. Epub 2008 Apr 11.
PMID: 18405974
citation: Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology. 2004 Mar;111(3):440-6. doi: 10.1016/j.ophtha.2003.06.020.
PMID: 15019316
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Seok Hyun Yun
investigator title: Professor of Dermatology
mesh term: Corneal Diseases
sharing ipd: No
provided document: 