<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/NCT04488887</url>
  </required_header>
  <id_info>
    <org_study_id>33875/6/20</org_study_id>
    <nct_id>NCT04488887</nct_id>
  </id_info>
  <brief_title>OCTA Metrics Repeatability and Reproducibility in Different Disorders</brief_title>
  <official_title>Evaluation of the Repeatability and Reproducibility of Different Quantitative Optical Coherence Tomography Angiography Metrics in Retinal Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tanta University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tanta University</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>
      Retinal imaging is a corner stone in diagnosis of most retinal disorders. Standard imaging&#xD;
      techniques e.g. fluorescein angiography and color fundus photography have a lot of&#xD;
      limitations including limited resolution, invasive nature in cases of fluorescein&#xD;
      angiography, and inability to segment the retina, accordingly, and only 2D image is provided.&#xD;
&#xD;
      Optical coherence tomography angiography (OCTA) is a recent noninvasive imaging technique&#xD;
      that allows for volumetric visualization of eye vasculature. OCTA has shown promise in better&#xD;
      elucidating the pathophysiology of several retinal vascular diseases. Swept-source OCTA uses&#xD;
      long wavelength ̰ 1,050nm, which can penetrate through deeper layers of the eye and can&#xD;
      traverse opacities of media such as cataracts, hemorrhages and vitreous opacities.&#xD;
&#xD;
      Optical coherence tomographic angiograms can further be manually or automatically segmented&#xD;
      with preprogrammed software to highlight individual layers of the retina, optic nerve head&#xD;
      choriocapillaris, and choroid. The user can either analyze en face images extending from the&#xD;
      inner limiting membrane to choroid or use automated views to locate a vascular or structural&#xD;
      lesion within the retina.&#xD;
&#xD;
      Different quantitative metrics has been extracted from enface OCTA images including vessel&#xD;
      density, FAZ area, choriocapillaries flow deficit, intercapillary area and fractal dimension.&#xD;
      These metrics are helpful in evaluation the retinal perfusion and used by physicians to&#xD;
      assess various retinal vascular disorders.&#xD;
&#xD;
      Although some previous literatures had discussed the repeatability of OCTA metrics, however,&#xD;
      comprehensive evaluation of widely used metrics in various retinal condition has not be done.&#xD;
      Additionally, recent data suggest that various methods of calculation of these metrics my&#xD;
      yield final different results of the same metric.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be prospective cross-sectional study. This research will be done in the period&#xD;
      between 1 August and 31 December 2020 and will include 80 eyes from patients with following&#xD;
      disorders:&#xD;
&#xD;
      Group 1: Patients with diabetic retinopathy Group 2: Patients with myopia Group 3: patients&#xD;
      with choroidal neovascularization Group 4: control eyes with no retinal disease. Inclusion&#xD;
      criteria: Patients above 18 years in age with any of above retinal condition and clear media&#xD;
      allowing for imaging will be included.&#xD;
&#xD;
      Exclusion criteria will include; Maculopathies (hereditary or acquired), optic nerve head&#xD;
      pathologies (tilted disc, drusen, optic disc edema, atrophy, etc.), optic neuropathies&#xD;
      (demyelinating, infectious, ischemic, etc.), adjusted IOP for central corneal thickness more&#xD;
      than 21 mmHg, surgery-induced corneal edema and dense cataracts that can disrupt images,&#xD;
      history of vasoactive agents (calcium antagonists, nitric oxide, etc.) use, systemic diseases&#xD;
      (vasculitis, diabetes mellitus, hypertension, etc.) and any previous ocular surgery, patients&#xD;
      with bad quality images or complicated surgeries will be excluded.&#xD;
&#xD;
      All patients will be subject to Full ophthalmologic examination and OCTA imaging.&#xD;
      High-quality 3 x 3 mm and 6 x 6 mm OCTA macular scans and 4.5 × 4.5-mm papillary scan with&#xD;
      strong signal-noise ratio and adequate centration on the fovea and optic nerve head&#xD;
      respectively will be selected.&#xD;
&#xD;
      For each patient 10 successive scans will be generated to allow for the analysis of&#xD;
      repeatability. Patient will be imaged in the same day at two different OCTA devices Dri&#xD;
      Triton (Topcon, Japan) and Cirrus OCT (Zeiss, USA) to investigate the reproducibility of the&#xD;
      measurements.&#xD;
&#xD;
      Automated segmentation will be used to evaluate superﬁcial and deep capillary retinal plexus&#xD;
      projections. If errors in segmentation were detected, manual correction would be performed.&#xD;
      The superﬁcial retinal capillary plexus (SCP) was delineated with an inner boundary at the&#xD;
      internal limiting membrane (ILM) and an outer boundary 10 µm inside the inner plexiform layer&#xD;
      (IPL). The deep retinal capillary plexus (DCP) was segmented with an inner boundary 10 µm&#xD;
      inside the IPL and an outer boundary at 10 µm beneath the outer plexiform layer (OPL). In&#xD;
      addition, the total retinal capillary plexus (TCP) was manually customized by selecting the&#xD;
      inner boundary at the ILM and the outer boundary set at 40 µm above the retinal pigment&#xD;
      epithelium (RPE) to avoid any ﬂow signals from choriocapillaries.&#xD;
&#xD;
      We will evaluate the following metric from enface OCT angiogram; vessel density, vessel&#xD;
      density, intercapillary area, fractal dimension and skeletonized vessel density.&#xD;
&#xD;
      Every included patient in this study will have unique code number referring to the file where&#xD;
      all his data will be kept confidential. Only macula and optic disc will be imaged.&#xD;
      Additionally, patients' personal data will be hidden during using of these images. All&#xD;
      patients' data will be used for scientific research only and will be kept totally&#xD;
      confidential. Comprehensive explanation of all aspects of this study will be given to&#xD;
      patients before their participation in it, an informed consent will be obtained from the&#xD;
      patients before their enrolment in the study. Although no documented adverse effects from&#xD;
      OCTA imaging on the patients to date, however, any unexpected risks appeared during the&#xD;
      research will be cleared to the participants and the ethical committee on time.&#xD;
&#xD;
      Statistical analysis will be performed using SPSS software (version 25; SPSS, Inc., Chicago,&#xD;
      IL, USA). the intraclass correlation coefficient (ICC) and coefficient of variation (CV) will&#xD;
      be calculated. ICC is the correlation between two variables measured at the same time point,&#xD;
      with values ranging from 0 to 1 (&lt;0.40, poor; 0.40-0.59, fair; 0.60-0.74, good; 0.75-1.00,&#xD;
      excellent). The CV (%) will be calculated as 100 × standard deviation/overall mean, and a&#xD;
      value &lt;10% represents good repeatability of the measurement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The intraclass correlation coefficient (ICC)</measure>
    <time_frame>5 months</time_frame>
    <description>ICC is the correlation between two variables measured at the same time point, with values ranging from 0 to 1 (&lt;0.40, poor; 0.40-0.59, fair; 0.60-0.74, good; 0.75-1.00, excellent).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>coefficient of variation (CV)</measure>
    <time_frame>5 months</time_frame>
    <description>The CV (%) will be calculated as 100 × standard deviation/overall mean, and a value &lt;10% represents good repeatability of the measurement.</description>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Diabetic Retinopathy</condition>
  <condition>Myopia</condition>
  <condition>Choroidal Neovascularization</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Diabetic retinopathy Group</arm_group_label>
    <description>Patients with non-proliferative and proliferative diabetic retinopathy with clear media will be recruited.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myopia Group</arm_group_label>
    <description>Patients with different grades of myopia, with accurate segmentation will be recruited</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Choroidal neovascularization group</arm_group_label>
    <description>Patients with active choroidal vascularization without scarring will be recruited</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <description>Healthy individuals without retinal disorders will be included for comaprison</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Optical coherence tomography angiography</intervention_name>
    <description>patients in all groups will be examined with optical coherence tomography angiography, for every eye 3 macular and 3 papillary scans will be performed by two different OCTA machines, analysis will be carried out to evaluate the repeatability and reproducibility of the test</description>
    <arm_group_label>Choroidal neovascularization group</arm_group_label>
    <arm_group_label>Diabetic retinopathy Group</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Myopia Group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Repeatability and reproducibility of the different OCTA metrics will be carried out in the&#xD;
        following disorders; diabetic retinopathy, myopia, choroidal neovascularization, and in&#xD;
        healthy controls for comparison.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 18 years or above, that fall in any of the study groups&#xD;
&#xD;
          -  Clear media allowing for imaging&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Maculopathies (hereditary or acquired)&#xD;
&#xD;
          -  Optic nerve head pathologies (tilted disc, drusen, optic disc edema, atrophy, etc.)&#xD;
&#xD;
          -  Optic neuropathies (demyelinating, infectious, ischemic, etc.),&#xD;
&#xD;
          -  corneal edema and dense cataracts that can disrupt images&#xD;
&#xD;
          -  history of vasoactive agents (calcium antagonists, nitric oxide, etc.)&#xD;
&#xD;
          -  systemic diseases (vasculitis, diabetes mellitus, hypertension, etc.)&#xD;
&#xD;
          -  Previous ocular surgery&#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>Osama A Sorour, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tanta University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rauof A Gaber</last_name>
    <phone>+201012292208</phone>
    <email>dr.osamasorour@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ophthalmology Department, Faculty of medicine, Tanta Univeristy</name>
      <address>
        <city>Tanta</city>
        <zip>31515</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Mehta N, Liu K, Alibhai AY, Gendelman I, Braun PX, Ishibazawa A, Sorour O, Duker JS, Waheed NK. Impact of Binarization Thresholding and Brightness/Contrast Adjustment Methodology on Optical Coherence Tomography Angiography Image Quantification. Am J Ophthalmol. 2019 Sep;205:54-65. doi: 10.1016/j.ajo.2019.03.008. Epub 2019 Mar 15.</citation>
    <PMID>30885708</PMID>
  </reference>
  <reference>
    <citation>Byon I, Alagorie AR, Ji Y, Su L, Sadda SR. Optimizing the Repeatability of Choriocapillaris Flow Deficit Measurement From Optical Coherence Tomography Angiography. Am J Ophthalmol. 2020 Nov;219:21-32. doi: 10.1016/j.ajo.2020.05.027. Epub 2020 May 23.</citation>
    <PMID>32454035</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 24, 2020</last_update_submitted>
  <last_update_submitted_qc>July 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tanta University</investigator_affiliation>
    <investigator_full_name>Osama Abdelfattah Sorour</investigator_full_name>
    <investigator_title>Retina Consultant &amp; the principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Retinopathy</mesh_term>
    <mesh_term>Choroidal Neovascularization</mesh_term>
    <mesh_term>Neovascularization, Pathologic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04488887
org study id: 33875/6/20
nct id: NCT04488887
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Retinal imaging is a corner stone in diagnosis of most retinal disorders. Standard imaging
      techniques e.g. fluorescein angiography and color fundus photography have a lot of
      limitations including limited resolution, invasive nature in cases of fluorescein
      angiography, and inability to segment the retina, accordingly, and only 2D image is provided.

      Optical coherence tomography angiography (OCTA) is a recent noninvasive imaging technique
      that allows for volumetric visualization of eye vasculature. OCTA has shown promise in better
      elucidating the pathophysiology of several retinal vascular diseases. Swept-source OCTA uses
      long wavelength ̰ 1,050nm, which can penetrate through deeper layers of the eye and can
      traverse opacities of media such as cataracts, hemorrhages and vitreous opacities.

      Optical coherence tomographic angiograms can further be manually or automatically segmented
      with preprogrammed software to highlight individual layers of the retina, optic nerve head
      choriocapillaris, and choroid. The user can either analyze en face images extending from the
      inner limiting membrane to choroid or use automated views to locate a vascular or structural
      lesion within the retina.

      Different quantitative metrics has been extracted from enface OCTA images including vessel
      density, FAZ area, choriocapillaries flow deficit, intercapillary area and fractal dimension.
      These metrics are helpful in evaluation the retinal perfusion and used by physicians to
      assess various retinal vascular disorders.

      Although some previous literatures had discussed the repeatability of OCTA metrics, however,
      comprehensive evaluation of widely used metrics in various retinal condition has not be done.
      Additionally, recent data suggest that various methods of calculation of these metrics my
      yield final different results of the same metric.
This will be prospective cross-sectional study. This research will be done in the period
      between 1 August and 31 December 2020 and will include 80 eyes from patients with following
      disorders:

      Group 1: Patients with diabetic retinopathy Group 2: Patients with myopia Group 3: patients
      with choroidal neovascularization Group 4: control eyes with no retinal disease. Inclusion
      criteria: Patients above 18 years in age with any of above retinal condition and clear media
      allowing for imaging will be included.

      Exclusion criteria will include; Maculopathies (hereditary or acquired), optic nerve head
      pathologies (tilted disc, drusen, optic disc edema, atrophy, etc.), optic neuropathies
      (demyelinating, infectious, ischemic, etc.), adjusted IOP for central corneal thickness more
      than 21 mmHg, surgery-induced corneal edema and dense cataracts that can disrupt images,
      history of vasoactive agents (calcium antagonists, nitric oxide, etc.) use, systemic diseases
      (vasculitis, diabetes mellitus, hypertension, etc.) and any previous ocular surgery, patients
      with bad quality images or complicated surgeries will be excluded.

      All patients will be subject to Full ophthalmologic examination and OCTA imaging.
      High-quality 3 x 3 mm and 6 x 6 mm OCTA macular scans and 4.5 × 4.5-mm papillary scan with
      strong signal-noise ratio and adequate centration on the fovea and optic nerve head
      respectively will be selected.

      For each patient 10 successive scans will be generated to allow for the analysis of
      repeatability. Patient will be imaged in the same day at two different OCTA devices Dri
      Triton (Topcon, Japan) and Cirrus OCT (Zeiss, USA) to investigate the reproducibility of the
      measurements.

      Automated segmentation will be used to evaluate superﬁcial and deep capillary retinal plexus
      projections. If errors in segmentation were detected, manual correction would be performed.
      The superﬁcial retinal capillary plexus (SCP) was delineated with an inner boundary at the
      internal limiting membrane (ILM) and an outer boundary 10 µm inside the inner plexiform layer
      (IPL). The deep retinal capillary plexus (DCP) was segmented with an inner boundary 10 µm
      inside the IPL and an outer boundary at 10 µm beneath the outer plexiform layer (OPL). In
      addition, the total retinal capillary plexus (TCP) was manually customized by selecting the
      inner boundary at the ILM and the outer boundary set at 40 µm above the retinal pigment
      epithelium (RPE) to avoid any ﬂow signals from choriocapillaries.

      We will evaluate the following metric from enface OCT angiogram; vessel density, vessel
      density, intercapillary area, fractal dimension and skeletonized vessel density.

      Every included patient in this study will have unique code number referring to the file where
      all his data will be kept confidential. Only macula and optic disc will be imaged.
      Additionally, patients' personal data will be hidden during using of these images. All
      patients' data will be used for scientific research only and will be kept totally
      confidential. Comprehensive explanation of all aspects of this study will be given to
      patients before their participation in it, an informed consent will be obtained from the
      patients before their enrolment in the study. Although no documented adverse effects from
      OCTA imaging on the patients to date, however, any unexpected risks appeared during the
      research will be cleared to the participants and the ethical committee on time.

      Statistical analysis will be performed using SPSS software (version 25; SPSS, Inc., Chicago,
      IL, USA). the intraclass correlation coefficient (ICC) and coefficient of variation (CV) will
      be calculated. ICC is the correlation between two variables measured at the same time point,
      with values ranging from 0 to 1 (<0.40, poor; 0.40-0.59, fair; 0.60-0.74, good; 0.75-1.00,
      excellent). The CV (%) will be calculated as 100 × standard deviation/overall mean, and a
      value <10% represents good repeatability of the measurement.
observational model: Case-Control
time perspective: Prospective
measure: The intraclass correlation coefficient (ICC)
time frame: 5 months
description: ICC is the correlation between two variables measured at the same time point, with values ranging from 0 to 1 (<0.40, poor; 0.40-0.59, fair; 0.60-0.74, good; 0.75-1.00, excellent).
measure: coefficient of variation (CV)
time frame: 5 months
description: The CV (%) will be calculated as 100 × standard deviation/overall mean, and a value <10% represents good repeatability of the measurement.
arm group label: Diabetic retinopathy Group
description: Patients with non-proliferative and proliferative diabetic retinopathy with clear media will be recruited.
arm group label: Myopia Group
description: Patients with different grades of myopia, with accurate segmentation will be recruited
arm group label: Choroidal neovascularization group
description: Patients with active choroidal vascularization without scarring will be recruited
arm group label: Healthy controls
description: Healthy individuals without retinal disorders will be included for comaprison
intervention type: Diagnostic Test
intervention name: Optical coherence tomography angiography
description: patients in all groups will be examined with optical coherence tomography angiography, for every eye 3 macular and 3 papillary scans will be performed by two different OCTA machines, analysis will be carried out to evaluate the repeatability and reproducibility of the test
arm group label: Choroidal neovascularization group
arm group label: Diabetic retinopathy Group
arm group label: Healthy controls
arm group label: Myopia Group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Osama A Sorour, MD
role: Principal Investigator
affiliation: Tanta University
last name: Rauof A Gaber
phone: +201012292208
email: dr.osamasorour@gmail.com
facility: 
country: Egypt
citation: Mehta N, Liu K, Alibhai AY, Gendelman I, Braun PX, Ishibazawa A, Sorour O, Duker JS, Waheed NK. Impact of Binarization Thresholding and Brightness/Contrast Adjustment Methodology on Optical Coherence Tomography Angiography Image Quantification. Am J Ophthalmol. 2019 Sep;205:54-65. doi: 10.1016/j.ajo.2019.03.008. Epub 2019 Mar 15.
PMID: 30885708
citation: Byon I, Alagorie AR, Ji Y, Su L, Sadda SR. Optimizing the Repeatability of Choriocapillaris Flow Deficit Measurement From Optical Coherence Tomography Angiography. Am J Ophthalmol. 2020 Nov;219:21-32. doi: 10.1016/j.ajo.2020.05.027. Epub 2020 May 23.
PMID: 32454035
responsible party type: Principal Investigator
investigator affiliation: Tanta University
investigator full name: Osama Abdelfattah Sorour
investigator title: Retina Consultant & the principal investigator
mesh term: Diabetic Retinopathy
mesh term: Choroidal Neovascularization
mesh term: Neovascularization, Pathologic
sharing ipd: No