<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/NCT04417959</url>
  </required_header>
  <id_info>
    <org_study_id>AUH_øjensygdomme_DSAEK_vs_DMEK</org_study_id>
    <nct_id>NCT04417959</nct_id>
  </id_info>
  <brief_title>A Comparison of Visual Functions and Side-effects After DSAEK or DMEK for Fuchs' Endothelial Dystrophy</brief_title>
  <official_title>A Comparison of Visual Functions and Side-effects After DSAEK or DMEK for Fuchs' Endothelial Dystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane&#xD;
      endothelial keratoplasty (DMEK) are becoming increasingly popular as treatments for Fuchs'&#xD;
      endothelial dystrophy. However, despite several years of use the incidence of cystoid macular&#xD;
      edema and damage related to increased intraocular pressure (IOP), and the forward scattering&#xD;
      of light through the eye following DSAEK or DMEK have to our knowledge not been prospectively&#xD;
      described. Therefore, this project will be a randomized controlled trial investigating these&#xD;
      matters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose:&#xD;
&#xD;
      To investigate 3 different side-effects after DSAEK, DMEK, and cataract extraction (CE) in a&#xD;
      randomized controlled trial with 12 months follow-up with CE as an additional control group.&#xD;
&#xD;
        1. To investigate the extend of subclinical cystoid macular edema (CME) and epiretinal&#xD;
           membrane (ERM) after DSAEK, DMEK, and CE.&#xD;
&#xD;
        2. To investigate IOP-related changes after DSAEK, DMEK, and CE in means of pupil diameter&#xD;
           and cpRNFLT. Further, to describe iris alterations including Urrets-Zavalia Syndrome&#xD;
           (UZS).&#xD;
&#xD;
        3. To compare the difference in forward scatter, visual acuity (VA), and low-contrast VA&#xD;
           after DSAEK, DMEK, and CE and relate this to the best corrected visual acuity (BCVA).&#xD;
           Further, to investigate changes in higher-order aberrations, patient reported outcome&#xD;
           measures (PROM), and total corneal refraction after the procedures.&#xD;
&#xD;
      Hypotheses:&#xD;
&#xD;
        1. Subclinical CME and ERM are adverse effects that occur equally often following DSAEK,&#xD;
           DMEK, and CE.&#xD;
&#xD;
        2. Following DSAEK, DMEK, and CE, there are no differences in the amount of IOP-related&#xD;
           changes in means of pupil diameter,cpRNFLT thinning or iris alterations.&#xD;
&#xD;
        3. Changes in OSI, HOA, PROM, VA, contrast sensitivity, and total corneal refraction occur&#xD;
           to the same extend after DSAEK, DMEK, and CE.&#xD;
&#xD;
      Materials and Methods:&#xD;
&#xD;
      Patients referred to the Department of Ophthalmology at Aarhus University Hospital (AUH) for&#xD;
      EK or CE will be assessed in order to identify suitable study subjects.&#xD;
&#xD;
      Only patients with primary endothelial failure (Fuchs endothelial dystrophy) and a&#xD;
      concomitant need for CE will be considered eligible for randomization to either the DSAEK or&#xD;
      the DMEK study groups. Patients included in the study will be randomized 1:1 to the DSAEK or&#xD;
      DMEK study groups. Patients referred for CE will be offered to participate in the project and&#xD;
      will be included in the CE group. Based on power calculations, it is planned to include 40&#xD;
      patients in each of the 3 groups.&#xD;
&#xD;
      Subject and donor characteristics will be gathered. Subjects with prior uveitis, severe&#xD;
      vitreous opacities, diabetes, retinal vein occlusion, glaucoma, age-related macular&#xD;
      degeneration, macular atrophy, trauma or corneal grafting will be excluded from the study.&#xD;
      Data collection will be conducted at AUH before the interventions and in the follow-up&#xD;
      period.&#xD;
&#xD;
      Donor tissue will be prepared in the Danish Cornea Bank, either pre-pealed for DMEK or&#xD;
      pre-cut for DSAEK.&#xD;
&#xD;
      Measurements as described below will be conducted both prior to the surgical intervention and&#xD;
      3, 6, and 12 months after this.&#xD;
&#xD;
      Patients lost to follow-up during the project will only be used for analysis at the&#xD;
      time-point they have attended. Therefore, for all time-points after the loss to follow-up&#xD;
      these subjects will be excluded from our investigation.&#xD;
&#xD;
      In case of capsule rupture where the intraocular lens still is positioned into the lens bag&#xD;
      during CE or if rebubbling is needed after DSAEK or DMEK, the subjects will still be eligible&#xD;
      for further participation in the project. Adverse events such as primary graft failure or&#xD;
      rejection is considered to be rare events for both DSAEK and DMEK and subjects with these&#xD;
      will be excluded from our final estimates.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</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>Study subjects with the requirement for endothelial keratoplasty and a concomitant need for cataract extraction will be randomized 1:1 to either phaco-DSAEK or phaco-DMEK. Further, a third group consisting of sujects with a solely need for cataract extraction will be included as a control group in our study. The three groups will be prospectively followed.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Subjects randomized to either phaco-DSAEK or phaco-DMEK will be blinded in the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Best corrected visual acuity (BCVA)</measure>
    <time_frame>12 months</time_frame>
    <description>BCVA will be measured using the early treatment diabetic retinopathy study (ETDRS) chart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cystoid macular edema</measure>
    <time_frame>3 months</time_frame>
    <description>This will be quantified as central retinal thickness (µm) measured using optical coherence tomography (OCT) scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Largest pupil diameter (mm)</measure>
    <time_frame>12 months</time_frame>
    <description>The pupil diameter will be measured using the pupillometer DP-2000, Neuroptics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iris contraction velocity (mm/s)</measure>
    <time_frame>12 months</time_frame>
    <description>The contraction velocity will be measured using the pupillometer DP-2000, Neuroptics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circumpapillary Retinal Nerve Fibre Layer Thickness (cpRNFLT) (µm)</measure>
    <time_frame>12 months</time_frame>
    <description>The cpRNFLT will be measured using OCT-scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Contrast-sensitivity (Weber contrast units)</measure>
    <time_frame>12 months</time_frame>
    <description>This will be measured using the Freiburg Visual Acuity and Contrast Test (FrACT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forward light scatter</measure>
    <time_frame>12 months</time_frame>
    <description>Forward light scatter will be measured using the HD Analyzer, Optical Quality Analysis System (OQAS), Visiometrics. The forward light scatter will be assessed using the objective scattering index (OSI). This system evaluates the intraocular scattering of light.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Higher-order aberrations (HOA) (µm)</measure>
    <time_frame>12 months</time_frame>
    <description>Measurements will be performed using Pentacam, Oculus. HOA will be quantified as the root mean square (RMS).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Epiretinal membrane (ERM) formation</measure>
    <time_frame>12 months</time_frame>
    <description>Formation and changes will be assessed using OCT-scans.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Fuchs' Endothelial Dystrophy</condition>
  <arm_group>
    <arm_group_label>Phaco-DSAEK</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects randomized to this arm will consist of patients with both Fuchs' endothelial dystrophy and cataract. These will be treated with phacoemulsification and Descemet's stripping automated endothelial keratoplasty.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phaco-DMEK</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects randomized to this arm will consist of patients with both Fuchs' endothelial dystrophy and cataract. These will be treated with phacoemulsification and Descemet's membrane endothelial keratoplasty.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Phaco-DSAEK</intervention_name>
    <description>The intervention will be performed as a DSAEK triple-procedure with phacoemulsification and intraocular lens implantation prior to DSAEK.</description>
    <arm_group_label>Phaco-DSAEK</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Phaco-DMEK</intervention_name>
    <description>The intervention will be performed as a DMEK triple-procedure with phacoemulsification and intraocular lens implantation prior to DMEK.</description>
    <arm_group_label>Phaco-DMEK</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cataract and/or&#xD;
&#xD;
          -  Fuch's endothelial dystrophy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uveitis&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Retinal vein occlusion&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Exudative age-related macular degeneration&#xD;
&#xD;
          -  Advanced macular atrophy&#xD;
&#xD;
          -  Ocular trauma&#xD;
&#xD;
          -  Prior corneal grafting&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Ophthalmology</name>
      <address>
        <city>Aarhus</city>
        <state>Region Midtjylland</state>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fuchs' Endothelial Dystrophy</mesh_term>
  </condition_browse>
  <!-- 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/NCT04417959
org study id: AUH_øjensygdomme_DSAEK_vs_DMEK
nct id: NCT04417959
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane
      endothelial keratoplasty (DMEK) are becoming increasingly popular as treatments for Fuchs'
      endothelial dystrophy. However, despite several years of use the incidence of cystoid macular
      edema and damage related to increased intraocular pressure (IOP), and the forward scattering
      of light through the eye following DSAEK or DMEK have to our knowledge not been prospectively
      described. Therefore, this project will be a randomized controlled trial investigating these
      matters.
Purpose:

      To investigate 3 different side-effects after DSAEK, DMEK, and cataract extraction (CE) in a
      randomized controlled trial with 12 months follow-up with CE as an additional control group.

        1. To investigate the extend of subclinical cystoid macular edema (CME) and epiretinal
           membrane (ERM) after DSAEK, DMEK, and CE.

        2. To investigate IOP-related changes after DSAEK, DMEK, and CE in means of pupil diameter
           and cpRNFLT. Further, to describe iris alterations including Urrets-Zavalia Syndrome
           (UZS).

        3. To compare the difference in forward scatter, visual acuity (VA), and low-contrast VA
           after DSAEK, DMEK, and CE and relate this to the best corrected visual acuity (BCVA).
           Further, to investigate changes in higher-order aberrations, patient reported outcome
           measures (PROM), and total corneal refraction after the procedures.

      Hypotheses:

        1. Subclinical CME and ERM are adverse effects that occur equally often following DSAEK,
           DMEK, and CE.

        2. Following DSAEK, DMEK, and CE, there are no differences in the amount of IOP-related
           changes in means of pupil diameter,cpRNFLT thinning or iris alterations.

        3. Changes in OSI, HOA, PROM, VA, contrast sensitivity, and total corneal refraction occur
           to the same extend after DSAEK, DMEK, and CE.

      Materials and Methods:

      Patients referred to the Department of Ophthalmology at Aarhus University Hospital (AUH) for
      EK or CE will be assessed in order to identify suitable study subjects.

      Only patients with primary endothelial failure (Fuchs endothelial dystrophy) and a
      concomitant need for CE will be considered eligible for randomization to either the DSAEK or
      the DMEK study groups. Patients included in the study will be randomized 1:1 to the DSAEK or
      DMEK study groups. Patients referred for CE will be offered to participate in the project and
      will be included in the CE group. Based on power calculations, it is planned to include 40
      patients in each of the 3 groups.

      Subject and donor characteristics will be gathered. Subjects with prior uveitis, severe
      vitreous opacities, diabetes, retinal vein occlusion, glaucoma, age-related macular
      degeneration, macular atrophy, trauma or corneal grafting will be excluded from the study.
      Data collection will be conducted at AUH before the interventions and in the follow-up
      period.

      Donor tissue will be prepared in the Danish Cornea Bank, either pre-pealed for DMEK or
      pre-cut for DSAEK.

      Measurements as described below will be conducted both prior to the surgical intervention and
      3, 6, and 12 months after this.

      Patients lost to follow-up during the project will only be used for analysis at the
      time-point they have attended. Therefore, for all time-points after the loss to follow-up
      these subjects will be excluded from our investigation.

      In case of capsule rupture where the intraocular lens still is positioned into the lens bag
      during CE or if rebubbling is needed after DSAEK or DMEK, the subjects will still be eligible
      for further participation in the project. Adverse events such as primary graft failure or
      rejection is considered to be rare events for both DSAEK and DMEK and subjects with these
      will be excluded from our final estimates.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Study subjects with the requirement for endothelial keratoplasty and a concomitant need for cataract extraction will be randomized 1:1 to either phaco-DSAEK or phaco-DMEK. Further, a third group consisting of sujects with a solely need for cataract extraction will be included as a control group in our study. The three groups will be prospectively followed.
primary purpose: Treatment
masking: Single (Participant)
masking description: Subjects randomized to either phaco-DSAEK or phaco-DMEK will be blinded in the study.
measure: Best corrected visual acuity (BCVA)
time frame: 12 months
description: BCVA will be measured using the early treatment diabetic retinopathy study (ETDRS) chart.
measure: Cystoid macular edema
time frame: 3 months
description: This will be quantified as central retinal thickness (µm) measured using optical coherence tomography (OCT) scans.
measure: Largest pupil diameter (mm)
time frame: 12 months
description: The pupil diameter will be measured using the pupillometer DP-2000, Neuroptics.
measure: Iris contraction velocity (mm/s)
time frame: 12 months
description: The contraction velocity will be measured using the pupillometer DP-2000, Neuroptics.
measure: Circumpapillary Retinal Nerve Fibre Layer Thickness (cpRNFLT) (µm)
time frame: 12 months
description: The cpRNFLT will be measured using OCT-scans.
measure: Contrast-sensitivity (Weber contrast units)
time frame: 12 months
description: This will be measured using the Freiburg Visual Acuity and Contrast Test (FrACT)
measure: Forward light scatter
time frame: 12 months
description: Forward light scatter will be measured using the HD Analyzer, Optical Quality Analysis System (OQAS), Visiometrics. The forward light scatter will be assessed using the objective scattering index (OSI). This system evaluates the intraocular scattering of light.
measure: Higher-order aberrations (HOA) (µm)
time frame: 12 months
description: Measurements will be performed using Pentacam, Oculus. HOA will be quantified as the root mean square (RMS).
measure: Epiretinal membrane (ERM) formation
time frame: 12 months
description: Formation and changes will be assessed using OCT-scans.
arm group label: Phaco-DSAEK
arm group type: Other
description: Subjects randomized to this arm will consist of patients with both Fuchs' endothelial dystrophy and cataract. These will be treated with phacoemulsification and Descemet's stripping automated endothelial keratoplasty.
arm group label: Phaco-DMEK
arm group type: Other
description: Subjects randomized to this arm will consist of patients with both Fuchs' endothelial dystrophy and cataract. These will be treated with phacoemulsification and Descemet's membrane endothelial keratoplasty.
intervention type: Procedure
intervention name: Phaco-DSAEK
description: The intervention will be performed as a DSAEK triple-procedure with phacoemulsification and intraocular lens implantation prior to DSAEK.
arm group label: Phaco-DSAEK
intervention type: Procedure
intervention name: Phaco-DMEK
description: The intervention will be performed as a DMEK triple-procedure with phacoemulsification and intraocular lens implantation prior to DMEK.
arm group label: Phaco-DMEK
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Fuchs' Endothelial Dystrophy