<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/NCT03841253</url>
  </required_header>
  <id_info>
    <org_study_id>LO007</org_study_id>
    <nct_id>NCT03841253</nct_id>
  </id_info>
  <brief_title>Treatment of Vision Disturbances Due to Corneal Irregularities by Trans-epithelial Optical Phototherapeutic Keratectomy (TE-oPTK)</brief_title>
  <official_title>Treatment of Vision Disturbances Due to Corneal Irregularities by Trans-epithelial Optical Phototherapeutic Keratectomy (TE-oPTK)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>London Vision Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Optana GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>London Vision Clinic</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study sets out to evaluate the EpiMaster application software for use in predicting the&#xD;
      refractive change induced by a trans-epithelial phototherapeutic keratectomy (TE-PTK)&#xD;
      procedure in eyes with irregularly irregular astigmatism. If validation criteria are met&#xD;
      during the observational phase, the software refractive prediction will be used to plan the&#xD;
      refractive correction in TE-PTK treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Complications after laser eye surgery can often result in the front surface of the eye (the&#xD;
      cornea) becoming irregular, which causes visual symptoms such as halos, glare, starbursts,&#xD;
      double vision, and reduced contrast sensitivity. For the past 20 years, corneal&#xD;
      irregularities have been treated using wavefront-guided ablation, topography-guided ablation&#xD;
      or trans-epithelial phototherapeutic keratectomy (TE-PTK). Topography-guided ablation is the&#xD;
      most effective treatment for certain types of irregularity and works by using a laser to&#xD;
      remove tissue from the cornea in a pattern derived from a topography scan (a measurement of&#xD;
      the shape and curvature of the front of the eye) designed to make the corneal surface more&#xD;
      regular.&#xD;
&#xD;
      However, topography-guided ablation is less effective for other types of irregularity. In&#xD;
      these cases, the corneal epithelium (the layer of skin on the surface of the cornea) has&#xD;
      changed in thickness to partially hide the irregularity on the body of the cornea under the&#xD;
      epithelium (the stroma). The epithelium does this by becoming thinner over peaks and&#xD;
      thickening over troughs in the stroma. Therefore, the topography measurement can only detect&#xD;
      the proportion of the irregularity that has not been hidden by the epithelium, hence reducing&#xD;
      its effectiveness. The preferred treatment option is TE-PTK; the laser treatment is applied&#xD;
      onto and through the epithelium, breaking through to the stroma where the epithelium is&#xD;
      thinnest, thus removing tissue from the peaks on the stroma resulting in a more regular&#xD;
      surface.&#xD;
&#xD;
      The main weakness of TE-PTK is that it may unpredictably change the refraction to become more&#xD;
      short-sighted or more long-sighted or change the astigmatism. To improve this, we have&#xD;
      developed the Epimaster software that simulates a TE-PTK treatment and predicts the change in&#xD;
      refraction.&#xD;
&#xD;
      The aim of the study is to validate the refractive prediction produced by the Epimaster&#xD;
      software by comparing this to the achieved result in the patients treated. The treatment&#xD;
      received by the patient will be the same as has been used routinely for the past 20 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Anticipated">March 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">March 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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Phase 1 will be observational comparing the software predicted refractive change to the observed refractive change.&#xD;
Phase 2 will use the software predicted refractive change to plan the refractive component of the treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The tendency of manifest sphere, cylinder and axis</measure>
    <time_frame>3-12 months</time_frame>
    <description>The correct tendency of manifest sphere, cylinder and axis should be achieved in 90% of cases, where tendency refers to:&#xD;
The sign of the predicted and the post-operative sphere is equal for predicted sphere values greater than absolute value 0.50 D (confidence limit)&#xD;
The sign of the predicted and the post-operative cylinder is equal (same cylinder format setting like e.g. plus cylinder format) for predicted cylinder values greater than absolute value 0.50 D (confidence limit)&#xD;
The cylinder axis of the predicted and the post-operative cylinder do not deviate by more than ±45° for predicted cylinder values greater than absolute value 0.50 D (confidence limit)&#xD;
In none of the cases the prediction in sphere and cylinder is more than absolute value 2.00 D off the post-operative values.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Standard deviation of SEpostop-SEpredicted</measure>
    <time_frame>12 months</time_frame>
    <description>Standard deviation of SEpostop-SEpredicted at each follow-up time point (represents the scatter of the refractive outcome), where SEpredicted is the refractive outcome predicted by the EpiMaster application software.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Corneal Astigmatism</condition>
  <arm_group>
    <arm_group_label>Observation Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A trans-epithelial PTK procedure will be performed using the MEL 90 excimer laser. The refractive outcome will be compared to the refractive change predicted by the EpiMaster application software.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>If the transition criteria are met during the observational phase, the treatment phase will be initiated. A trans-epithelial PTK procedure will be performed using the MEL 90 excimer laser, including a refractive component according to the values determined using the EpiMaster application software.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Trans-epithelial PTK</intervention_name>
    <description>The MEL 90 excimer laser will be used to ablate the corneal epithelium and stroma to a pre-defined depth, using the epithelium as a natural masking agent to smooth the stromal surface.</description>
    <arm_group_label>Observation Phase</arm_group_label>
    <arm_group_label>Treatment Phase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EpiMaster Application Software</intervention_name>
    <description>The EpiMaster Application Software imports epithelial thickness data and corneal front surface topography data, and uses this to calculate the refractive change that would be induced by a trans-epithelial PTK treatment.</description>
    <arm_group_label>Observation Phase</arm_group_label>
    <arm_group_label>Treatment Phase</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient presents with topographic irregularly irregular astigmatism and associated&#xD;
             quality of vision issues, where TE-PTK would be a more effective treatment than&#xD;
             topography-guided ablation or other therapeutic treatment options.&#xD;
&#xD;
        Medically suitable for corneal laser refractive surgery.&#xD;
&#xD;
          -  Calculated residual stromal thickness ≥250 µm.&#xD;
&#xD;
          -  Subjects should be 21 years of age or older.&#xD;
&#xD;
          -  Contact lens wearers must stop wearing their contact lenses one week per decade of&#xD;
             wear before baseline measurements in case of hard contact lenses and one week before&#xD;
             baseline measurements in case of soft contact lenses.&#xD;
&#xD;
          -  Patient will be able to understand the patient information and willing to sign an&#xD;
             informed consent.&#xD;
&#xD;
          -  Patient will be willing to comply with all follow-up visits and the respective&#xD;
             examinations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient not being able to tolerate local or topical anesthesia&#xD;
&#xD;
          -  Autoimmune diseases&#xD;
&#xD;
          -  Sicca syndrome, dry eye&#xD;
&#xD;
          -  Herpes viral (herpes simplex) infections&#xD;
&#xD;
          -  Herpes zoster&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Pregnant or nursing women (or who are planning pregnancy during the study)&#xD;
&#xD;
          -  Patients with a weight of &gt; 135 kg&#xD;
&#xD;
          -  Any residual, recurrent or acute ocular disease or abnormality of the eye, e.g.&#xD;
&#xD;
          -  Cataract&#xD;
&#xD;
          -  Suspected glaucoma or an intraocular pressure &gt; 21 mm of Hg&#xD;
&#xD;
          -  Corneal disease&#xD;
&#xD;
          -  Corneal thinning disorder, e.g. keratoconus,&#xD;
&#xD;
          -  Pellucid marginal corneal degeneration&#xD;
&#xD;
          -  Dystrophy of the basal membrane&#xD;
&#xD;
          -  Corneal oedema&#xD;
&#xD;
          -  Exudative macular degeneration&#xD;
&#xD;
          -  Infection&#xD;
&#xD;
          -  Any residual, recurrent, or active abnormality of the cornea to be treated, e.g.&#xD;
&#xD;
          -  Existing corneal implant&#xD;
&#xD;
          -  Corneal lesion&#xD;
&#xD;
          -  Unstable refraction&#xD;
&#xD;
          -  Connective tissue disease&#xD;
&#xD;
          -  Dry eye&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Timothy J Archer, PhD</last_name>
    <phone>02072241005</phone>
    <email>tim@londonvisionclinic.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>London Vision Clinic</name>
      <address>
        <city>London</city>
        <zip>W1G 7LA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Timothy Archer, MA</last_name>
      <phone>02072241005</phone>
      <email>tim@londonvisionclinic.com</email>
    </contact>
    <investigator>
      <last_name>Dan Z Reinstein, MD, MA, FRCOphth</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Reinstein DZ, Archer TJ, Gobbe M. Refractive and topographic errors in topography-guided ablation produced by epithelial compensation predicted by 3D Artemis VHF digital ultrasound stromal and epithelial thickness mapping. J Refract Surg. 2012 Sep;28(9):657-63. doi: 10.3928/1081597X-20120815-02.</citation>
    <PMID>22947295</PMID>
  </reference>
  <reference>
    <citation>Reinstein DZ, Archer TJ, Gobbe M. Improved effectiveness of transepithelial PTK versus topography-guided ablation for stromal irregularities masked by epithelial compensation. J Refract Surg. 2013 Aug;29(8):526-33. doi: 10.3928/1081597X-20130719-02.</citation>
    <PMID>23909779</PMID>
  </reference>
  <reference>
    <citation>Reinstein DZ, Archer TJ, Dickeson ZI, Gobbe M. Transepithelial phototherapeutic keratectomy protocol for treating irregular astigmatism based on population epithelial thickness measurements by artemis very high-frequency digital ultrasound. J Refract Surg. 2014 Jun;30(6):380-7. doi: 10.3928/1081597X-20140508-01.</citation>
    <PMID>24972404</PMID>
  </reference>
  <reference>
    <citation>Guglielmetti S, Kirton A, Reinstein DZ, Carp GI, Archer TJ. Repair of Irregularly Irregular Astigmatism by Transepithelial Phototherapeutic Keratectomy. J Refract Surg. 2017 Oct 1;33(10):714-719. doi: 10.3928/1081597X-20170721-04.</citation>
    <PMID>28991341</PMID>
  </reference>
  <reference>
    <citation>Reinstein DZ, Archer T. Combined Artemis very high-frequency digital ultrasound-assisted transepithelial phototherapeutic keratectomy and wavefront-guided treatment following multiple corneal refractive procedures. J Cataract Refract Surg. 2006 Nov;32(11):1870-6. doi: 10.1016/j.jcrs.2006.07.016.</citation>
    <PMID>17081871</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>February 12, 2019</study_first_submitted>
  <study_first_submitted_qc>February 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Trans-epithelial phototherapeutic keratectomy</keyword>
  <keyword>PTK</keyword>
  <keyword>TE-PTK</keyword>
  <keyword>Corneal epithelium</keyword>
  <keyword>Excimer laser</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Astigmatism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Participant data will not be shared with other researchers.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03841253
org study id: LO007
nct id: NCT03841253
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study sets out to evaluate the EpiMaster application software for use in predicting the
      refractive change induced by a trans-epithelial phototherapeutic keratectomy (TE-PTK)
      procedure in eyes with irregularly irregular astigmatism. If validation criteria are met
      during the observational phase, the software refractive prediction will be used to plan the
      refractive correction in TE-PTK treatments.
Complications after laser eye surgery can often result in the front surface of the eye (the
      cornea) becoming irregular, which causes visual symptoms such as halos, glare, starbursts,
      double vision, and reduced contrast sensitivity. For the past 20 years, corneal
      irregularities have been treated using wavefront-guided ablation, topography-guided ablation
      or trans-epithelial phototherapeutic keratectomy (TE-PTK). Topography-guided ablation is the
      most effective treatment for certain types of irregularity and works by using a laser to
      remove tissue from the cornea in a pattern derived from a topography scan (a measurement of
      the shape and curvature of the front of the eye) designed to make the corneal surface more
      regular.

      However, topography-guided ablation is less effective for other types of irregularity. In
      these cases, the corneal epithelium (the layer of skin on the surface of the cornea) has
      changed in thickness to partially hide the irregularity on the body of the cornea under the
      epithelium (the stroma). The epithelium does this by becoming thinner over peaks and
      thickening over troughs in the stroma. Therefore, the topography measurement can only detect
      the proportion of the irregularity that has not been hidden by the epithelium, hence reducing
      its effectiveness. The preferred treatment option is TE-PTK; the laser treatment is applied
      onto and through the epithelium, breaking through to the stroma where the epithelium is
      thinnest, thus removing tissue from the peaks on the stroma resulting in a more regular
      surface.

      The main weakness of TE-PTK is that it may unpredictably change the refraction to become more
      short-sighted or more long-sighted or change the astigmatism. To improve this, we have
      developed the Epimaster software that simulates a TE-PTK treatment and predicts the change in
      refraction.

      The aim of the study is to validate the refractive prediction produced by the Epimaster
      software by comparing this to the achieved result in the patients treated. The treatment
      received by the patient will be the same as has been used routinely for the past 20 years.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Phase 1 will be observational comparing the software predicted refractive change to the observed refractive change.
Phase 2 will use the software predicted refractive change to plan the refractive component of the treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: The tendency of manifest sphere, cylinder and axis
time frame: 3-12 months
description: The correct tendency of manifest sphere, cylinder and axis should be achieved in 90% of cases, where tendency refers to:
The sign of the predicted and the post-operative sphere is equal for predicted sphere values greater than absolute value 0.50 D (confidence limit)
The sign of the predicted and the post-operative cylinder is equal (same cylinder format setting like e.g. plus cylinder format) for predicted cylinder values greater than absolute value 0.50 D (confidence limit)
The cylinder axis of the predicted and the post-operative cylinder do not deviate by more than ±45° for predicted cylinder values greater than absolute value 0.50 D (confidence limit)
In none of the cases the prediction in sphere and cylinder is more than absolute value 2.00 D off the post-operative values.
measure: Standard deviation of SEpostop-SEpredicted
time frame: 12 months
description: Standard deviation of SEpostop-SEpredicted at each follow-up time point (represents the scatter of the refractive outcome), where SEpredicted is the refractive outcome predicted by the EpiMaster application software.
arm group label: Observation Phase
arm group type: Experimental
description: A trans-epithelial PTK procedure will be performed using the MEL 90 excimer laser. The refractive outcome will be compared to the refractive change predicted by the EpiMaster application software.
arm group label: Treatment Phase
arm group type: Experimental
description: If the transition criteria are met during the observational phase, the treatment phase will be initiated. A trans-epithelial PTK procedure will be performed using the MEL 90 excimer laser, including a refractive component according to the values determined using the EpiMaster application software.
intervention type: Procedure
intervention name: Trans-epithelial PTK
description: The MEL 90 excimer laser will be used to ablate the corneal epithelium and stroma to a pre-defined depth, using the epithelium as a natural masking agent to smooth the stromal surface.
arm group label: Observation Phase
arm group label: Treatment Phase
intervention type: Device
intervention name: EpiMaster Application Software
description: The EpiMaster Application Software imports epithelial thickness data and corneal front surface topography data, and uses this to calculate the refractive change that would be induced by a trans-epithelial PTK treatment.
arm group label: Observation Phase
arm group label: Treatment Phase
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Timothy J Archer, PhD
phone: 02072241005
email: tim@londonvisionclinic.com
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
citation: Reinstein DZ, Archer TJ, Gobbe M. Refractive and topographic errors in topography-guided ablation produced by epithelial compensation predicted by 3D Artemis VHF digital ultrasound stromal and epithelial thickness mapping. J Refract Surg. 2012 Sep;28(9):657-63. doi: 10.3928/1081597X-20120815-02.
PMID: 22947295
citation: Reinstein DZ, Archer TJ, Gobbe M. Improved effectiveness of transepithelial PTK versus topography-guided ablation for stromal irregularities masked by epithelial compensation. J Refract Surg. 2013 Aug;29(8):526-33. doi: 10.3928/1081597X-20130719-02.
PMID: 23909779
citation: Reinstein DZ, Archer TJ, Dickeson ZI, Gobbe M. Transepithelial phototherapeutic keratectomy protocol for treating irregular astigmatism based on population epithelial thickness measurements by artemis very high-frequency digital ultrasound. J Refract Surg. 2014 Jun;30(6):380-7. doi: 10.3928/1081597X-20140508-01.
PMID: 24972404
citation: Guglielmetti S, Kirton A, Reinstein DZ, Carp GI, Archer TJ. Repair of Irregularly Irregular Astigmatism by Transepithelial Phototherapeutic Keratectomy. J Refract Surg. 2017 Oct 1;33(10):714-719. doi: 10.3928/1081597X-20170721-04.
PMID: 28991341
citation: Reinstein DZ, Archer T. Combined Artemis very high-frequency digital ultrasound-assisted transepithelial phototherapeutic keratectomy and wavefront-guided treatment following multiple corneal refractive procedures. J Cataract Refract Surg. 2006 Nov;32(11):1870-6. doi: 10.1016/j.jcrs.2006.07.016.
PMID: 17081871
responsible party type: Sponsor
mesh term: Astigmatism
sharing ipd: No
ipd description: Participant data will not be shared with other researchers.