<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/NCT04426175</url>
  </required_header>
  <id_info>
    <org_study_id>CPFEM-0007-DE</org_study_id>
    <nct_id>NCT04426175</nct_id>
  </id_info>
  <brief_title>Z8 OCT-controlled 2D vs 3D LASIK</brief_title>
  <official_title>Precision of 2D vs 3D Low Energy Femto-LASIK: Intraoperative and Postoperative OCT-based Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zentrumsehstarke Hamburg</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zentrumsehstarke Hamburg</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study was to test the hypothesis that OCT-guided 110 µm targeted flaps will&#xD;
      result in accurate, predictable, and precise thickness flaps, with low complication rates&#xD;
      when performed and compared using both 2D and 3D flap geometry applications and how it&#xD;
      correlated to visual experience and quality of life responses during the early postoperative&#xD;
      period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It has been postulated that it is possible with the Ziemer Femtosecond LDV laser system to&#xD;
      create reproducible flaps in terms of thickness and predictability. The aim of this study was&#xD;
      to test the hypothesis that OCT-guided 110 µm targeted flaps will result in accurate,&#xD;
      predictable, and precise thickness flaps, with low complication rates when performed and&#xD;
      compared using both 2D and 3D flap geometry applications. Patient-reported outcomes are&#xD;
      increasingly incorporated into clinical trials as they provide access to valuable information&#xD;
      on the physical experience of the patient during and after the treatment. A questionnaire&#xD;
      will therefore also be introduced in this study to evaluate how well self-reported pain,&#xD;
      visual experience, and quality of life responses are correlated with flap geometries in both&#xD;
      groups during the early postoperative period. The study holds direct medical benefit to the&#xD;
      patient in this that they received an immediate improvement in his/her unaided vision.&#xD;
      Moreover, the patient's participation contributes to the medical knowledge about the use of&#xD;
      femtosecond lasers for refractive surgery, in particular in view of the use of intraoperative&#xD;
      OCT visualization tools. The patients will gain access to the newest technology available for&#xD;
      refractive surgery namely a low pulse energy high-frequency femtosecond laser.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2019</start_date>
  <completion_date type="Actual">April 23, 2020</completion_date>
  <primary_completion_date type="Actual">April 23, 2020</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Predictability of central flap thickness in OCT-controlled 110 µm LASIK</measure>
    <time_frame>1 month postoperatively</time_frame>
    <description>Analyze central flap thickness in OCT-controlled 110 µm LASIK and to report on intended versus achieved flap thickness of one group with a 2D flap geometry in one eye and another group with a 3D flap geometry in the contralateral eye. All OCT measurements will be done in micron metres (µm).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of intraoperative flap thickness with pre- and postoperative results</measure>
    <time_frame>1 week, 1 month</time_frame>
    <description>Measurement of corneal thickness pre flap creation (Corneal Pachymetry measurements expressed in µm indicate the thickness of the cornea before flap was created. This measurement will serve as the baseline measurement. Pachymetry measured again after the flap was created and lifted by means of optical and ultrasonic pachymetry(µm) for both groups and to be compare with postoperative AS-OCT measurements also measured in µm.This will indicate how accurate the intraoperative flap thickness compare to the 1 week and 1 month thickness measurements as swelling and inflammatory processes could influence postoperative measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative planarity</measure>
    <time_frame>1 week, 1 month</time_frame>
    <description>Assessment of several measurements taken along the corneal cut on superior, nasal, inferior and temporal points in order to compare the uniformity of the cut between 2D vs 3D geometries. Measurments will be done by means of AS-OCT,measured in µm units.Measurements at two different follow up periods will be analyzed and compared in order to rule out the role that inflammation could possibly play.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative flap morphology</measure>
    <time_frame>During surgery</time_frame>
    <description>Observations that are defined by different scales in order to report on important features pertaining to 2D and 3D intraoperative flap geometries eg. the presence and extent of opaque bubble layer (OBL), ease of flap lifting and stromal bed quality in both groups . Intraoperative flap morphology assessment to be done as soon as the flap was created in terms of presence of an opaque bubble layer (no OBL, 30-40% of flap surface, &gt;40% of flap surface). Once the flap was lifted to report on ease of flap lifting (easy/sticky/can not lift) and to describe the stromal bed quality (smooth,tissue bridges, rastered, lines).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative flap properties</measure>
    <time_frame>1 week, 1 month</time_frame>
    <description>Evaluate flap properties by means of slit lamp biomicroscopy examination. The flap's visual appearance seen with the slit lamp to be described and documented as per the suggested scales during 2 specified follow up visits in terms of edge quality and visibility ('yes/no' If yes= extreme fine line, distinct line or irregular edge), border shape (round, irregular) and interface quality (smooth, lines, cobblestones, grids, microstriae) and be compared between flap geometries (2D and 3D flaps).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual outcomes</measure>
    <time_frame>1 day, 1 week, 1 month</time_frame>
    <description>Compare pre- and postoperative visual acuity (UDVA, CDVA) measurements by means of a Snellen Visual Acuity chart and be expressed in decimal that will be converted to logMar units for the purpose of statistical analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient reported Outcomes: early recovery period</measure>
    <time_frame>1 day, 2Day, 1 week follow up</time_frame>
    <description>Conduct a non validated Patient Reported Outcome (PRO) questionnaire adopted and based on the 'Brief Pain Inventory' questionnaire [Porela-Tiihonen] to assess patient's early visual perceptions and pain experience related to their own functional status and wellbeing and to compare between the two eyes since each undergone different cutting geometry (2D vs 3D) methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications</measure>
    <time_frame>Intra- and postoperatively up to 1 month follow up</time_frame>
    <description>Report and document any intra- and postoperative complications that may occur during the time of the procedure or at the 1 month follow up visit.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Myopia</condition>
  <condition>Astigmatism</condition>
  <arm_group>
    <arm_group_label>2D LASIK</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>With the 2D method, the flap resection is created in a planar mode (xy-plane), without vertical cut, at the requested depth.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3D LASIK</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>With the 3D method, the flap resection is done in a three-dimensional mode, at the requested depth, with the requested diameter and the desired border (side cut) angle</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>2D and 3D cutting method using a low energy Femtosecond laser LDV Z8 for LASIK flap cutting</intervention_name>
    <description>2D and 3D cutting methods were randomly used in same subjects</description>
    <arm_group_label>2D LASIK</arm_group_label>
    <arm_group_label>3D LASIK</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Key inclusion criteria as described by the German Commission for Refractive Surgery (KRC)&#xD;
        are:&#xD;
&#xD;
          -  The recommended range of application for the correction of myopia is up to -8.00 D and&#xD;
             for the correction of astigmatism up to 5.00 D.&#xD;
&#xD;
          -  The limited for LASIK correction of myopia is up to -10.00 D and correction of&#xD;
             astigmatism up to 6.00 D. If myopic astigmatism is to be corrected, the values for&#xD;
             myopia and astigmatism must be added together.&#xD;
&#xD;
          -  The recommended range for correction of hyperopia is up to 3.00 D. Up to 4.00 D is the&#xD;
             range of limited application for hyperopia.&#xD;
&#xD;
          -  Age ≥18 years with stable eyesight for over 12 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Key exclusion criteria as described by the German Commission for Refractive Surgery (KRC):&#xD;
&#xD;
          -  preoperative corneal thickness less than 480 μm&#xD;
&#xD;
          -  predicted stromal thickness under the flap after ablation of less than 250 μm&#xD;
&#xD;
          -  chronic progressive corneal disease and forme fruste keratoconus&#xD;
&#xD;
          -  surgery before the age of 18 years&#xD;
&#xD;
          -  symptomatic cataract&#xD;
&#xD;
          -  Glaucoma with a marked loss of visual field&#xD;
&#xD;
          -  Exudative macular degeneration.&#xD;
&#xD;
          -  Concurrent participation in another ophthalmological clinical study&#xD;
&#xD;
        Exclusion criteria irrespective of the KRC criteria:&#xD;
&#xD;
          -  Undergone former eye surgery&#xD;
&#xD;
          -  Contact lens wear within the two weeks prior to commencement of preoperative&#xD;
             measurements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephan Linke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zentrumsehstarke Hamburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zentrumsehstärke</name>
      <address>
        <city>Hamburg</city>
        <zip>20251</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Huhtala A, Pietila J, Makinen P, Uusitalo H. Femtosecond lasers for laser in situ keratomileusis: a systematic review and meta-analysis. Clin Ophthalmol. 2016 Mar 7;10:393-404. doi: 10.2147/OPTH.S99394. eCollection 2016.</citation>
    <PMID>27022236</PMID>
  </reference>
  <reference>
    <citation>Eldaly ZH, Abdelsalam MA, Hussein MS, Nassr MA. Comparison of Laser In Situ Keratomileusis Flap Morphology and Predictability by WaveLight FS200 Femtosecond Laser and Moria Microkeratome: An Anterior Segment Optical Coherence Tomography Study. Korean J Ophthalmol. 2019 Apr;33(2):113-121. doi: 10.3341/kjo.2018.0035.</citation>
    <PMID>30977320</PMID>
  </reference>
  <reference>
    <citation>Pajic B, Vastardis I, Pajic-Eggspuehler B, Gatzioufas Z, Hafezi F. Femtosecond laser versus mechanical microkeratome-assisted flap creation for LASIK: a prospective, randomized, paired-eye study. Clin Ophthalmol. 2014 Sep 22;8:1883-9. doi: 10.2147/OPTH.S68124. eCollection 2014.</citation>
    <PMID>25284975</PMID>
  </reference>
  <reference>
    <citation>Tomita M, Chiba A, Matsuda J, Nawa Y. Evaluation of LASIK treatment with the Femto LDV in patients with corneal opacity. J Refract Surg. 2012 Jan;28(1):25-30. doi: 10.3928/1081597X-20111213-01. Epub 2011 Dec 19.</citation>
    <PMID>22185466</PMID>
  </reference>
  <reference>
    <citation>Pietila J, Huhtala A, Makinen P, Uusitalo H. Flap characteristics, predictability, and safety of the Ziemer FEMTO LDV femtosecond laser with the disposable suction ring for LASIK. Eye (Lond). 2014 Jan;28(1):66-71. doi: 10.1038/eye.2013.244. Epub 2013 Nov 15.</citation>
    <PMID>24232315</PMID>
  </reference>
  <reference>
    <citation>Pietila J, Huhtala A, Makinen P, Salmenhaara K, Uusitalo H. Laser-assisted in situ keratomileusis flap creation with the three-dimensional, transportable Ziemer FEMTO LDV model Z6 I femtosecond laser. Acta Ophthalmol. 2014 Nov;92(7):650-5. doi: 10.1111/aos.12333. Epub 2013 Dec 26.</citation>
    <PMID>24373615</PMID>
  </reference>
  <reference>
    <citation>Porela-Tiihonen S, Kaarniranta K, Kokki M, Purhonen S, Kokki H. A prospective study on postoperative pain after cataract surgery. Clin Ophthalmol. 2013;7:1429-35. doi: 10.2147/OPTH.S47576. Epub 2013 Jul 15.</citation>
    <PMID>23885165</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Femtosecond Laser Assisted Laser in Situ Keratomileusis</keyword>
  <keyword>LASIK</keyword>
  <keyword>FEMTO LDV Z8</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>It is not clear yet to what extend IPD will be implemented. Patient privacy and confidentiality are the most important factors to consider. We consider sharing limited information upon request.</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/NCT04426175
org study id: CPFEM-0007-DE
nct id: NCT04426175
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study was to test the hypothesis that OCT-guided 110 µm targeted flaps will
      result in accurate, predictable, and precise thickness flaps, with low complication rates
      when performed and compared using both 2D and 3D flap geometry applications and how it
      correlated to visual experience and quality of life responses during the early postoperative
      period.
It has been postulated that it is possible with the Ziemer Femtosecond LDV laser system to
      create reproducible flaps in terms of thickness and predictability. The aim of this study was
      to test the hypothesis that OCT-guided 110 µm targeted flaps will result in accurate,
      predictable, and precise thickness flaps, with low complication rates when performed and
      compared using both 2D and 3D flap geometry applications. Patient-reported outcomes are
      increasingly incorporated into clinical trials as they provide access to valuable information
      on the physical experience of the patient during and after the treatment. A questionnaire
      will therefore also be introduced in this study to evaluate how well self-reported pain,
      visual experience, and quality of life responses are correlated with flap geometries in both
      groups during the early postoperative period. The study holds direct medical benefit to the
      patient in this that they received an immediate improvement in his/her unaided vision.
      Moreover, the patient's participation contributes to the medical knowledge about the use of
      femtosecond lasers for refractive surgery, in particular in view of the use of intraoperative
      OCT visualization tools. The patients will gain access to the newest technology available for
      refractive surgery namely a low pulse energy high-frequency femtosecond laser.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Predictability of central flap thickness in OCT-controlled 110 µm LASIK
time frame: 1 month postoperatively
description: Analyze central flap thickness in OCT-controlled 110 µm LASIK and to report on intended versus achieved flap thickness of one group with a 2D flap geometry in one eye and another group with a 3D flap geometry in the contralateral eye. All OCT measurements will be done in micron metres (µm).
measure: Comparison of intraoperative flap thickness with pre- and postoperative results
time frame: 1 week, 1 month
description: Measurement of corneal thickness pre flap creation (Corneal Pachymetry measurements expressed in µm indicate the thickness of the cornea before flap was created. This measurement will serve as the baseline measurement. Pachymetry measured again after the flap was created and lifted by means of optical and ultrasonic pachymetry(µm) for both groups and to be compare with postoperative AS-OCT measurements also measured in µm.This will indicate how accurate the intraoperative flap thickness compare to the 1 week and 1 month thickness measurements as swelling and inflammatory processes could influence postoperative measurements.
measure: Postoperative planarity
time frame: 1 week, 1 month
description: Assessment of several measurements taken along the corneal cut on superior, nasal, inferior and temporal points in order to compare the uniformity of the cut between 2D vs 3D geometries. Measurments will be done by means of AS-OCT,measured in µm units.Measurements at two different follow up periods will be analyzed and compared in order to rule out the role that inflammation could possibly play.
measure: Intraoperative flap morphology
time frame: During surgery
description: Observations that are defined by different scales in order to report on important features pertaining to 2D and 3D intraoperative flap geometries eg. the presence and extent of opaque bubble layer (OBL), ease of flap lifting and stromal bed quality in both groups . Intraoperative flap morphology assessment to be done as soon as the flap was created in terms of presence of an opaque bubble layer (no OBL, 30-40% of flap surface, >40% of flap surface). Once the flap was lifted to report on ease of flap lifting (easy/sticky/can not lift) and to describe the stromal bed quality (smooth,tissue bridges, rastered, lines).
measure: Postoperative flap properties
time frame: 1 week, 1 month
description: Evaluate flap properties by means of slit lamp biomicroscopy examination. The flap's visual appearance seen with the slit lamp to be described and documented as per the suggested scales during 2 specified follow up visits in terms of edge quality and visibility ('yes/no' If yes= extreme fine line, distinct line or irregular edge), border shape (round, irregular) and interface quality (smooth, lines, cobblestones, grids, microstriae) and be compared between flap geometries (2D and 3D flaps).
measure: Visual outcomes
time frame: 1 day, 1 week, 1 month
description: Compare pre- and postoperative visual acuity (UDVA, CDVA) measurements by means of a Snellen Visual Acuity chart and be expressed in decimal that will be converted to logMar units for the purpose of statistical analysis.
measure: Patient reported Outcomes: early recovery period
time frame: 1 day, 2Day, 1 week follow up
description: Conduct a non validated Patient Reported Outcome (PRO) questionnaire adopted and based on the 'Brief Pain Inventory' questionnaire [Porela-Tiihonen] to assess patient's early visual perceptions and pain experience related to their own functional status and wellbeing and to compare between the two eyes since each undergone different cutting geometry (2D vs 3D) methods.
measure: Complications
time frame: Intra- and postoperatively up to 1 month follow up
description: Report and document any intra- and postoperative complications that may occur during the time of the procedure or at the 1 month follow up visit.
arm group label: 2D LASIK
arm group type: Experimental
description: With the 2D method, the flap resection is created in a planar mode (xy-plane), without vertical cut, at the requested depth.
arm group label: 3D LASIK
arm group type: Experimental
description: With the 3D method, the flap resection is done in a three-dimensional mode, at the requested depth, with the requested diameter and the desired border (side cut) angle
intervention type: Device
intervention name: 2D and 3D cutting method using a low energy Femtosecond laser LDV Z8 for LASIK flap cutting
description: 2D and 3D cutting methods were randomly used in same subjects
arm group label: 2D LASIK
arm group label: 3D LASIK
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Stephan Linke, MD
role: Principal Investigator
affiliation: Zentrumsehstarke Hamburg
facility: 
country: Germany
citation: Huhtala A, Pietila J, Makinen P, Uusitalo H. Femtosecond lasers for laser in situ keratomileusis: a systematic review and meta-analysis. Clin Ophthalmol. 2016 Mar 7;10:393-404. doi: 10.2147/OPTH.S99394. eCollection 2016.
PMID: 27022236
citation: Eldaly ZH, Abdelsalam MA, Hussein MS, Nassr MA. Comparison of Laser In Situ Keratomileusis Flap Morphology and Predictability by WaveLight FS200 Femtosecond Laser and Moria Microkeratome: An Anterior Segment Optical Coherence Tomography Study. Korean J Ophthalmol. 2019 Apr;33(2):113-121. doi: 10.3341/kjo.2018.0035.
PMID: 30977320
citation: Pajic B, Vastardis I, Pajic-Eggspuehler B, Gatzioufas Z, Hafezi F. Femtosecond laser versus mechanical microkeratome-assisted flap creation for LASIK: a prospective, randomized, paired-eye study. Clin Ophthalmol. 2014 Sep 22;8:1883-9. doi: 10.2147/OPTH.S68124. eCollection 2014.
PMID: 25284975
citation: Tomita M, Chiba A, Matsuda J, Nawa Y. Evaluation of LASIK treatment with the Femto LDV in patients with corneal opacity. J Refract Surg. 2012 Jan;28(1):25-30. doi: 10.3928/1081597X-20111213-01. Epub 2011 Dec 19.
PMID: 22185466
citation: Pietila J, Huhtala A, Makinen P, Uusitalo H. Flap characteristics, predictability, and safety of the Ziemer FEMTO LDV femtosecond laser with the disposable suction ring for LASIK. Eye (Lond). 2014 Jan;28(1):66-71. doi: 10.1038/eye.2013.244. Epub 2013 Nov 15.
PMID: 24232315
citation: Pietila J, Huhtala A, Makinen P, Salmenhaara K, Uusitalo H. Laser-assisted in situ keratomileusis flap creation with the three-dimensional, transportable Ziemer FEMTO LDV model Z6 I femtosecond laser. Acta Ophthalmol. 2014 Nov;92(7):650-5. doi: 10.1111/aos.12333. Epub 2013 Dec 26.
PMID: 24373615
citation: Porela-Tiihonen S, Kaarniranta K, Kokki M, Purhonen S, Kokki H. A prospective study on postoperative pain after cataract surgery. Clin Ophthalmol. 2013;7:1429-35. doi: 10.2147/OPTH.S47576. Epub 2013 Jul 15.
PMID: 23885165
responsible party type: Sponsor
mesh term: Astigmatism
sharing ipd: No
ipd description: It is not clear yet to what extend IPD will be implemented. Patient privacy and confidentiality are the most important factors to consider. We consider sharing limited information upon request.