<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/NCT02208089</url>
  </required_header>
  <id_info>
    <org_study_id>ALLB1018</org_study_id>
    <nct_id>NCT02208089</nct_id>
  </id_info>
  <brief_title>Simultaneous TransPRK and Corneal Collagen Cross-Linking</brief_title>
  <acronym>TransPRKCXL</acronym>
  <official_title>A Prospective Trial of Simultaneous Combined Transepithelial Photorefractive Keratectomy and Corneal Collagen Cross-linking for Keratoconus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bruce Allan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Moorfields Eye Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Moorfields Eye Hospital NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Young patients with keratoconus face two problems: disease progression and corneal shape&#xD;
      irregularity leading to poor vision even in spectacles.&#xD;
&#xD;
      Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression&#xD;
      in keratoconus. The aim is to stiffen the cornea thereby preventing further shape&#xD;
      deterioration.&#xD;
&#xD;
      Topography or wavefront guided transepithelial photorefractive keratectomy (transPRK) uses&#xD;
      the excimer laser (the laser used to correct sight in 'laser eye surgery') to reduce corneal&#xD;
      shape irregularity in early stage keratoconus, reducing dependence on contact lenses.&#xD;
&#xD;
      In transPRK, the corneal skin layer is removed in a well controlled, no touch procedure,&#xD;
      preparing the cornea for CXL. Performing both treatments simultaneously (combining both&#xD;
      procedures in one operation) may offer several advantages over performing CXL first then&#xD;
      waiting for corneal shape to stabilise before performing transPRK. In particular, visual&#xD;
      rehabilitation may be faster. This study aims to evaluate visual recovery after simultaneous&#xD;
      CXL and transPRK in progressive early stage keratoconus. Visual recovery in these patients&#xD;
      will be compared with results for a similar group of patients with early stage keratoconus&#xD;
      who have already been treated with CXL alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Features which distinguish this trial from previous trials of combined photorefractive&#xD;
      keratectomy (PRK) and corneal collagen cross-linking (CXL) are: a rapid, pulsed light, CXL&#xD;
      protocol; and a treatment programming algorithm for PRK designed to target higher order&#xD;
      aberrations only with no compensatory additional laser corneal tissue removal.&#xD;
&#xD;
      Excimer laser treatment will be performed with the Schwind Amaris 750S laser&#xD;
      (www.eye-tech-solutions.com). Unique features of this system utilised here include:&#xD;
&#xD;
        -  Pre-programmed transepithelial ablation - laser removal of the minimum area of corneal&#xD;
           epithelium required for PRK promoting more rapid recovery than conventional methods (20%&#xD;
           alcohol application and manual epithelial removal). An 8mm diameter ablation zone will&#xD;
           be applied throughout.&#xD;
&#xD;
        -  Enhanced algorithms for minimal laser tissue removal - in this trial, the investigators&#xD;
           are targeting higher order aberrations only (coma in particular) with the aim of&#xD;
           improving spectacle corrected visual acuity without regard to the predicted&#xD;
           spherocylindrical outcome. Unlike other current excimer laser platforms, Schwind Amaris&#xD;
           treatment programming software allows treatment for irregular astigmatism without&#xD;
           additional compensatory laser tissue removal to correct the spherocylindrical change&#xD;
           induced by treatment of higher order aberrations. Higher order aberrations can also be&#xD;
           treated selectively. The investigators will use an algorithm step that targets only&#xD;
           aberrations (up to 6th order Zernike polynomials) with a value greater than 2 standard&#xD;
           deviations from the population mean in normative data. These treatment planning steps&#xD;
           allow the laser to create a large diameter treatment with minimal treatment depth.&#xD;
&#xD;
      Laser epithelial removal alone (transPTK at depth 55µm) removes a maximum 65µm of tissue in&#xD;
      the corneal periphery. For patients with 390µm at the thinnest point, transPTK will therefore&#xD;
      leave above 325µm residual stromal thickness prior to CXL. This is in line with&#xD;
      recommendations for minimum stromal thickness after epithelial removal in the CXL protocol&#xD;
      used here. Limited stromal reshaping is achieved in this simple embodiment of transPRK for&#xD;
      keratoconus by taking advantage of the masking effect of the corneal epithelium, which tends&#xD;
      to be thinnest over the cone apex. Where the thinnest point is greater than 390µm, further&#xD;
      reductions in corneal shape irregularity can be produced by adding either wavefront or&#xD;
      topography guided additional stromal ablation using custom programming on the Schwind Amaris&#xD;
      laser. Ocular wavefront (aberrometry) guided smoothing will be used for patients with a 5.5mm&#xD;
      or larger pupil at scanning and a consistent scan sequence (3 scans within 0.5 dioptre (D)&#xD;
      spherical equivalent refraction). Corneal wavefront (topography) guided smoothing will be&#xD;
      used for patients with ocular wavefront scans which do not meet these criteria. In all cases,&#xD;
      a minimum corneal stromal thickness prior to CXL of 325µm will be preserved.&#xD;
&#xD;
      Immediately after PRK, corneal collagen cross-linking will be performed using the following&#xD;
      protocol&#xD;
&#xD;
      Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation&#xD;
      (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation&#xD;
      to remove excess riboflavin prior to UV light exposure.&#xD;
&#xD;
      UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4&#xD;
      minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light&#xD;
      source)&#xD;
&#xD;
      Mitomycin C will not be used. A bandage contact lens will be applied at the end of treatment&#xD;
      and a standard post photorefractive keratectomy topical and systemic drug treatment regimen&#xD;
      will be used in every case with initial clinical review 1 week after surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Interventional case series with matched historical controls</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in LogMAR Corrected Distance Visual Acuity (CDVA)</measure>
    <time_frame>Preoperative vs 24 months</time_frame>
    <description>Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinically Significant Visual Gain</measure>
    <time_frame>Preoperative vs 24 months postoperative</time_frame>
    <description>Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinically Significant Visual Loss</measure>
    <time_frame>preoperative vs 24 months postoperative</time_frame>
    <description>Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map</measure>
    <time_frame>Preoperative vs 24 months postoperative</time_frame>
    <description>Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Rate</measure>
    <time_frame>6 months postoperative - 24 months postoperative</time_frame>
    <description>The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Keratoconus</condition>
  <arm_group>
    <arm_group_label>TransPRKCXL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CXL only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Corneal collagen cross-linking (CXL) using the same protocol without transepithelial photorefractive keratectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transepithelial Photorefractive Keratectomy (TransPRK)</intervention_name>
    <description>Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).</description>
    <arm_group_label>TransPRKCXL</arm_group_label>
    <other_name>Corneal surface excimer laser treatment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Corneal Collagen Cross-Linking (CXL)</intervention_name>
    <description>Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
    <arm_group_label>CXL only</arm_group_label>
    <arm_group_label>TransPRKCXL</arm_group_label>
    <other_name>Rapid corneal collagen cross-linking</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with progressive stage II or III keratoconus&#xD;
&#xD;
          -  CDVA &lt; 0.00 logMAR or subjective problems with spectacle corrected visual quality&#xD;
             (ghost images or light scatter symptoms)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active ocular surface disease&#xD;
&#xD;
          -  Minimum corneal thickness &lt;390µm (leaving 325µm residual stromal thickness after&#xD;
             transPTK - in line with minimum thickness recommendations for the study CXL protocol)&#xD;
&#xD;
          -  Vulnerable groups (patients whose capacity for giving informed consent to participate&#xD;
             in the trial may be impaired)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce D Allan, MD FRCOphth</last_name>
    <role>Principal Investigator</role>
    <affiliation>Moorfields Eye Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dan M Gore, FRCOphth</last_name>
    <role>Principal Investigator</role>
    <affiliation>Moorfields Eye Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moorfields Eye Hospital NHS Foundation Trust, 162 City Road</name>
      <address>
        <city>London</city>
        <zip>EC1V 2PD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye (Lond). 2013 Mar;27(3):329-39. doi: 10.1038/eye.2012.257. Epub 2012 Dec 21.</citation>
    <PMID>23258309</PMID>
  </reference>
  <reference>
    <citation>Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014 Feb;30(2):88-93. doi: 10.3928/1081597X-20140120-03.</citation>
    <PMID>24763473</PMID>
  </reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>November 23, 2017</results_first_submitted>
  <results_first_submitted_qc>September 3, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 8, 2019</results_first_posted>
  <last_update_submitted>September 3, 2018</last_update_submitted>
  <last_update_submitted_qc>September 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Moorfields Eye Hospital NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Bruce Allan</investigator_full_name>
    <investigator_title>Consultant Ophthalmic Surgeon</investigator_title>
  </responsible_party>
  <keyword>Keratoconus</keyword>
  <keyword>Corneal collagen cross-linking</keyword>
  <keyword>Photorefractive keratectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratoconus</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients with Stage I-III keratoconus and corrected vision &lt;20/20 were recruited. Recruitment period: August 2014-July2015. Location: dedicated keratoconus clinic at Moorfields Eye Hospital, London.</recruitment_details>
      <pre_assignment_details>63 eligible patients were screened; 11 declined to participate after discussing consent information; 5 patients were found to be ineligible because of insufficient residual corneal stromal depth following PRK programming, leaving 47 patients who were treated with TransPRK/CXL</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>TransPRKCXL</title>
          <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
        </group>
        <group group_id="P2">
          <title>CXL Only</title>
          <description>Patients treated with standard accelerated corneal collagen cross-linking (historical controls)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Matched historical control cases of CXL treated using the same CXL protocol as the TransPRKCXL group prior to commencement of recruitment. These control cases were consecutive cases with 2 year follow up data, matched for age, corneal pachymetry, and corneal curvature with the TransPRK group</population>
      <group_list>
        <group group_id="B1">
          <title>TransPRKCXL</title>
          <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
        </group>
        <group group_id="B2">
          <title>CXL Only</title>
          <description>Corneal collagen cross-linking (CXL), manual corneal epithelial removal, no excimer laser treatment&#xD;
CXL protocol was identical in both study arms. After corneal epithelial removal, a 10 minute soak with Vibex rapid (www.avedro.com) was followed by 8 minutes pulsed UV light using a uniform beam source (KXL - www.avedro.com) and a 1.5 second on/off cycle (7.2mJ/cm2 total energy @ 30mW/cm2 irradiance).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="47"/>
            <count group_id="B2" value="47"/>
            <count group_id="B3" value="94"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.6" spread="3.8"/>
                    <measurement group_id="B2" value="24.3" spread="4.3"/>
                    <measurement group_id="B3" value="24.5" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in LogMAR Corrected Distance Visual Acuity (CDVA)</title>
        <description>Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)</description>
        <time_frame>Preoperative vs 24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TransPRKCXL</title>
            <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
          </group>
          <group group_id="O2">
            <title>CXL Only</title>
            <description>CXL only (no PRK) using manual corneal epithelial removal and the same accelerated pulsed protocol as used in the TransPRK group</description>
          </group>
        </group_list>
        <measure>
          <title>Change in LogMAR Corrected Distance Visual Acuity (CDVA)</title>
          <description>Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)</description>
          <units>LogMAR CDVA</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.13" spread="0.2"/>
                    <measurement group_id="O2" value="-0.05" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = TransPRK produced no gains in vision over and above those produced by CXL only</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinically Significant Visual Gain</title>
        <description>Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart</description>
        <time_frame>Preoperative vs 24 months postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TransPRKCXL</title>
            <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
          </group>
          <group group_id="O2">
            <title>CXL Only</title>
            <description>Corneal collagen cross-linking (CXL), manual corneal epithelial removal, no excimer laser treatment&#xD;
CXL protocol was identical in both study arms. After corneal epithelial removal, a 10 minute soak with Vibex rapid (www.avedro.com) was followed by 8 minutes pulsed UV light using a uniform beam source (KXL - www.avedro.com) and a 1.5 second on/off cycle (7.2mJ/cm2 total energy @ 30mW/cm2 irradiance).</description>
          </group>
        </group_list>
        <measure>
          <title>Clinically Significant Visual Gain</title>
          <description>Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis = an equal proportion of patients in both study arms have clinically significant visual gains</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinically Significant Visual Loss</title>
        <description>Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA)</description>
        <time_frame>preoperative vs 24 months postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TransPRKCXL</title>
            <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
          </group>
          <group group_id="O2">
            <title>CXL Only</title>
            <description>Corneal collagen cross-linking (CXL), manual corneal epithelial removal, no excimer laser treatment&#xD;
CXL protocol was identical in both study arms. After corneal epithelial removal, a 10 minute soak with Vibex rapid (www.avedro.com) was followed by 8 minutes pulsed UV light using a uniform beam source (KXL - www.avedro.com) and a 1.5 second on/off cycle (7.2mJ/cm2 total energy @ 30mW/cm2 irradiance).</description>
          </group>
        </group_list>
        <measure>
          <title>Clinically Significant Visual Loss</title>
          <description>Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>null hypothesis = rates of clinically significant visual loss are equal for TransPRKCXL and CXL only</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority = no significant difference between rates of clinically significant visual loss between groups at the p≤0.05 level</non_inferiority_desc>
            <p_value>0.13</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map</title>
        <description>Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening</description>
        <time_frame>Preoperative vs 24 months postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TransPRKCXL</title>
            <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
          </group>
          <group group_id="O2">
            <title>CXL Only</title>
            <description>Corneal collagen cross-linking (CXL), manual corneal epithelial removal, no excimer laser treatment&#xD;
CXL protocol was identical in both study arms. After corneal epithelial removal, a 10 minute soak with Vibex rapid (www.avedro.com) was followed by 8 minutes pulsed UV light using a uniform beam source (KXL - www.avedro.com) and a 1.5 second on/off cycle (7.2mJ/cm2 total energy @ 30mW/cm2 irradiance).</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map</title>
          <description>Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening</description>
          <units>Dioptres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.5" spread="2.6"/>
                    <measurement group_id="O2" value="-0.54" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Rate</title>
        <description>The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de).</description>
        <time_frame>6 months postoperative - 24 months postoperative</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TransPRKCXL</title>
            <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
          </group>
          <group group_id="O2">
            <title>CXL Only</title>
            <description>Corneal collagen cross-linking (CXL), manual corneal epithelial removal, no excimer laser treatment&#xD;
CXL protocol was identical in both study arms. After corneal epithelial removal, a 10 minute soak with Vibex rapid (www.avedro.com) was followed by 8 minutes pulsed UV light using a uniform beam source (KXL - www.avedro.com) and a 1.5 second on/off cycle (7.2mJ/cm2 total energy @ 30mW/cm2 irradiance).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Rate</title>
          <description>The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years following the intervention</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TransPRKCXL</title>
          <description>Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)&#xD;
Transepithelial Photorefractive Keratectomy (TransPRK): Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
        </group>
        <group group_id="E2">
          <title>CXL Only</title>
          <description>Standard accelerated corneal collagen cross-linking (historical controls)&#xD;
Corneal Collagen Cross-Linking (CXL): Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.&#xD;
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal Infection</sub_title>
                <description>One patient did not attend early follow up and reported to the casualty service 3 weeks after surgery with a bandage contact lens still in situ and corneal infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Mr Bruce Allan</name_or_title>
      <organization>Moorfields Eye Hospital NHS Foundation Trust</organization>
      <phone>02075662320</phone>
      <email>bruce.allan@ucl.ac.uk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02208089
org study id: ALLB1018
nct id: NCT02208089
lead sponsor: 
collaborator: 
has dmc: Yes
Young patients with keratoconus face two problems: disease progression and corneal shape
      irregularity leading to poor vision even in spectacles.

      Corneal collagen cross-linking (CXL) is a new treatment designed to halt disease progression
      in keratoconus. The aim is to stiffen the cornea thereby preventing further shape
      deterioration.

      Topography or wavefront guided transepithelial photorefractive keratectomy (transPRK) uses
      the excimer laser (the laser used to correct sight in 'laser eye surgery') to reduce corneal
      shape irregularity in early stage keratoconus, reducing dependence on contact lenses.

      In transPRK, the corneal skin layer is removed in a well controlled, no touch procedure,
      preparing the cornea for CXL. Performing both treatments simultaneously (combining both
      procedures in one operation) may offer several advantages over performing CXL first then
      waiting for corneal shape to stabilise before performing transPRK. In particular, visual
      rehabilitation may be faster. This study aims to evaluate visual recovery after simultaneous
      CXL and transPRK in progressive early stage keratoconus. Visual recovery in these patients
      will be compared with results for a similar group of patients with early stage keratoconus
      who have already been treated with CXL alone.
Features which distinguish this trial from previous trials of combined photorefractive
      keratectomy (PRK) and corneal collagen cross-linking (CXL) are: a rapid, pulsed light, CXL
      protocol; and a treatment programming algorithm for PRK designed to target higher order
      aberrations only with no compensatory additional laser corneal tissue removal.

      Excimer laser treatment will be performed with the Schwind Amaris 750S laser
      (www.eye-tech-solutions.com). Unique features of this system utilised here include:

        -  Pre-programmed transepithelial ablation - laser removal of the minimum area of corneal
           epithelium required for PRK promoting more rapid recovery than conventional methods (20%
           alcohol application and manual epithelial removal). An 8mm diameter ablation zone will
           be applied throughout.

        -  Enhanced algorithms for minimal laser tissue removal - in this trial, the investigators
           are targeting higher order aberrations only (coma in particular) with the aim of
           improving spectacle corrected visual acuity without regard to the predicted
           spherocylindrical outcome. Unlike other current excimer laser platforms, Schwind Amaris
           treatment programming software allows treatment for irregular astigmatism without
           additional compensatory laser tissue removal to correct the spherocylindrical change
           induced by treatment of higher order aberrations. Higher order aberrations can also be
           treated selectively. The investigators will use an algorithm step that targets only
           aberrations (up to 6th order Zernike polynomials) with a value greater than 2 standard
           deviations from the population mean in normative data. These treatment planning steps
           allow the laser to create a large diameter treatment with minimal treatment depth.

      Laser epithelial removal alone (transPTK at depth 55µm) removes a maximum 65µm of tissue in
      the corneal periphery. For patients with 390µm at the thinnest point, transPTK will therefore
      leave above 325µm residual stromal thickness prior to CXL. This is in line with
      recommendations for minimum stromal thickness after epithelial removal in the CXL protocol
      used here. Limited stromal reshaping is achieved in this simple embodiment of transPRK for
      keratoconus by taking advantage of the masking effect of the corneal epithelium, which tends
      to be thinnest over the cone apex. Where the thinnest point is greater than 390µm, further
      reductions in corneal shape irregularity can be produced by adding either wavefront or
      topography guided additional stromal ablation using custom programming on the Schwind Amaris
      laser. Ocular wavefront (aberrometry) guided smoothing will be used for patients with a 5.5mm
      or larger pupil at scanning and a consistent scan sequence (3 scans within 0.5 dioptre (D)
      spherical equivalent refraction). Corneal wavefront (topography) guided smoothing will be
      used for patients with ocular wavefront scans which do not meet these criteria. In all cases,
      a minimum corneal stromal thickness prior to CXL of 325µm will be preserved.

      Immediately after PRK, corneal collagen cross-linking will be performed using the following
      protocol

      Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation
      (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation
      to remove excess riboflavin prior to UV light exposure.

      UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4
      minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light
      source)

      Mitomycin C will not be used. A bandage contact lens will be applied at the end of treatment
      and a standard post photorefractive keratectomy topical and systemic drug treatment regimen
      will be used in every case with initial clinical review 1 week after surgery.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Interventional case series with matched historical controls
primary purpose: Treatment
masking: None (Open Label)
measure: Change in LogMAR Corrected Distance Visual Acuity (CDVA)
time frame: Preoperative vs 24 months
description: Change in spectacle corrected logarithm minimum angle of resolution (LogMAR) distance visual acuity recorded in a 4m testing lane in photopic lighting conditions between baseline measurement and final review at 24 months (note that negative change = better vision; 0.1 logMAR units = 1 line on the test chart)
measure: Clinically Significant Visual Gain
time frame: Preoperative vs 24 months postoperative
description: Number of participants with gain of ≥2 lines (≥0.20 logMAR units) corrected distance visual acuity (CDVA) on a standard 5 letter per line EDTRS visual acuity testing chart
measure: Clinically Significant Visual Loss
time frame: preoperative vs 24 months postoperative
description: Number of participants with loss of ≥2 lines (≥0.20 LogMAR units) corrected distance visual acuity (CDVA)
measure: Change in Kmax - Maximum Local Anterior Corneal Surface Curvature on Tomography Map
time frame: Preoperative vs 24 months postoperative
description: Pentacam (www.oculus.de) measure: Maximum local curvature (Kmax). Reduction in dioptric value = corneal flattening
measure: Progression Rate
time frame: 6 months postoperative - 24 months postoperative
description: The number of participants with possible keratoconus disease progression after treatment defined by a ≥1.5D increase in Kmax, anterior and posterior K2 (maximum local corneal curvature, maximum anterior and posterior meridional corneal curvature) measured using a Pentacam HD corneal tomographer (www.oculus.de).
arm group label: TransPRKCXL
arm group type: Experimental
description: Simultaneous combined transepithelial photorefractive keratectomy (TransPRK) and corneal collagen cross-linking (CXL)
arm group label: CXL only
arm group type: Active Comparator
description: Corneal collagen cross-linking (CXL) using the same protocol without transepithelial photorefractive keratectomy
intervention type: Procedure
intervention name: Transepithelial Photorefractive Keratectomy (TransPRK)
description: Aberrometry or topography guided transepithelial photorefractive keratectomy (TransPRK) using the Schwind Amaris 750s excimer laser (www.eye-tech-solutions.com), an 8mm treatment diameter, and a tissue saving algorithm targeting selected higher order aberrations only. TransPRK will be followed immediately by corneal collagen cross-linking (CXL).
arm group label: TransPRKCXL
other name: Corneal surface excimer laser treatment
intervention type: Procedure
intervention name: Corneal Collagen Cross-Linking (CXL)
description: Riboflavin soak: 10 minutes total soak time; application of 0.1% riboflavin preparation (VibeX Rapid - www.avedro.com) each 2 minutes with gentle balanced salt solution irrigation to remove excess riboflavin prior to UV light exposure.
UV light exposure: Total treatment time 8 minutes (370nm wavelength; 30mW/cm2 irradiance; 4 minutes total UV exposure time, pulsed 1.5 seconds on 1.5 seconds off; Avedro KXL I light source)
arm group label: CXL only
arm group label: TransPRKCXL
other name: Rapid corneal collagen cross-linking
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Bruce D Allan, MD FRCOphth
role: Principal Investigator
affiliation: Moorfields Eye Hospital NHS Foundation Trust
last name: Dan M Gore, FRCOphth
role: Principal Investigator
affiliation: Moorfields Eye Hospital NHS Foundation Trust
facility: 
country: United Kingdom
citation: Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye (Lond). 2013 Mar;27(3):329-39. doi: 10.1038/eye.2012.257. Epub 2012 Dec 21.
PMID: 23258309
citation: Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014 Feb;30(2):88-93. doi: 10.3928/1081597X-20140120-03.
PMID: 24763473
responsible party type: Sponsor-Investigator
investigator affiliation: Moorfields Eye Hospital NHS Foundation Trust
investigator full name: Bruce Allan
investigator title: Consultant Ophthalmic Surgeon
mesh term: Keratoconus
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 