<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/NCT01711879</url>
  </required_header>
  <id_info>
    <org_study_id>12-1526</org_study_id>
    <nct_id>NCT01711879</nct_id>
  </id_info>
  <brief_title>Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma</brief_title>
  <official_title>Use of Intravitreal Aflibercept Injection for Neovascular Glaucoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This 52 week study will assess the use of intravitreal aflibercept injections in patients&#xD;
      with neovascular glaucoma (NVG) compared to standard of care panretinal photocoagulation.&#xD;
&#xD;
      The investigators hypothesize that the neovascularization of the iris and angle present in&#xD;
      neovascular glaucoma will resolve more quickly in eye treated with intravitreal aflibercept&#xD;
      injection alone and result in increased comfort and preservation of visual field as compared&#xD;
      to current standard of care utilizing pan-retinal photocoagulation. The advantages to&#xD;
      intravitreal aflibercept injection use could include resolution of NVI/NVA&#xD;
      (neovascularization of the iris/neovascularization of the angle) leading to quicker pain&#xD;
      relief and quicker lowering of IOP (intraocular pressure).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The two arms of this study will compare current common practice (initial intravitreal&#xD;
      anti-VEGF (vascular endothelial growth factor) to study treatment (VEGF) injection only) for&#xD;
      52 weeks.&#xD;
&#xD;
      This single center study will consist of 20 patients with NVG. Patients will be randomized&#xD;
      to:&#xD;
&#xD;
        -  Group A: A single injection of 2mg (0.05ml) intravitreal aflibercept injection at&#xD;
           baseline followed by standard of care laser with observation for a total of 52 weeks.&#xD;
&#xD;
      or&#xD;
&#xD;
        -  Group B: 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two&#xD;
           additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52&#xD;
           weeks.&#xD;
&#xD;
      Clinical assessment will include pain assessment (Universal Pain Scale), best corrected&#xD;
      visual acuity (ETDRS), ophthalmic examination, anterior segment assessment including number&#xD;
      of clock-hours of NVI/NVA, gonioscopy, anterior segment photography, visual field test&#xD;
      (Humphrey SITA- Standard 24-2), optic nerve OCT (Zeiss Cirrus Optic Disc Cube 200x200),&#xD;
      macular OCT (Cube scan 512 x 128 and 5 Line Raster), fluorescein angiography (initial iris&#xD;
      phase followed by standard retinal angiography), and concurrent medical/ocular medications.&#xD;
      Qualitative assessment of neovascularization will be made by the investigator based on&#xD;
      comparison to baseline angiography.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>2 year</time_frame>
    <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the incidence of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of Adverse Events</measure>
    <time_frame>2 year</time_frame>
    <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the severity of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate and Extent of Resolution of Neovascularization</measure>
    <time_frame>1 year</time_frame>
    <description>Compare between Groups A and B the Rate and extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraocular Pressure (mmHg) at Baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraocular Pressure (mmHg) at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>Mean intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Losing &gt; 5 Letters on Visual Acuity in Each Group A and Group B</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>Comparison between patients, groups A and B, that lost &gt; 5 letters on visual acuity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients in Each, Group A and Group B, Gaining &gt; 5 Letters on Visual Acuity</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>Comparison of patients in each, group A and group B, that gained &gt; 5 letters on visual acuity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Acuity at Baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of visual acuity between groups A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Visual Acuity at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>Comparison of visual acuity at Week 52 between groups A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the Visual Field Between Groups</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison of the Visual field s measured by HVF 24-2 SITA Standards between groups A and B</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure of the Optical Coherence Tomography(OCT) Outcomes</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>Evaluation of the Optical Coherence Tomography(OCT) outcomes (average retinal nerve fiber layer(RNFL) and central macular thickness), Compared between groups A and B.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Need for Surgical Intervention</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison between groups A and B and the need for surgical intervention in both arms during the follow-up period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Need for Additional IOP Lowering Medications</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison between groups A and B for the need of additional IOP lowering medications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extent of Resolution of Neovascularization Between Groups</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison of groups A and B and the extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Average Retinal Nerve Fiber Layer (RNFL)</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison between groups A and B of the average retinal nerve fiber layer (RNFL) as measured by Optical Coherence Tomography (OCT)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Neovascular Glaucoma</condition>
  <arm_group>
    <arm_group_label>Aflibercept with Laser</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>Details covered in arm description</description>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_label>Aflibercept with Laser</arm_group_label>
    <other_name>Eylea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of neovascular glaucoma (Stage I-II)&#xD;
&#xD;
          -  Individuals who are ages 21-90 years old; male or female of any race&#xD;
&#xD;
          -  Presence of neovascularization of the iris and/or angle&#xD;
&#xD;
          -  At least 90 degrees of &quot;unzipped&quot; anterior chamber angle as noted by gonioscopy. (a&#xD;
             &quot;zipped angle is the term used for a drainage angle that is slowly closing due to scar&#xD;
             tissue from the neovascularization process)&#xD;
&#xD;
          -  Visual acuity of light perception or better in the study eye&#xD;
&#xD;
          -  Willing and able to comply with clinic visits and study-related procedures&#xD;
&#xD;
          -  Provide signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of intravitreal anti-VEGF agents in the study eye in the past 3 months.&#xD;
&#xD;
          -  Full PRP in the study eye&#xD;
&#xD;
          -  Prior vitrectomy in the study eye&#xD;
&#xD;
          -  Prior trabeculectomy or other filtration surgery in the study eye&#xD;
&#xD;
          -  Active ocular or periocular infection in the study eye&#xD;
&#xD;
          -  Ocular conditions (Cataract or vitreous hemorrhage) that might require surgery in next&#xD;
             12 months&#xD;
&#xD;
          -  Allergy to fluorescein dye&#xD;
&#xD;
          -  Any past use of systemic anti-VEGF medication&#xD;
&#xD;
          -  Myocardial infarction within 6 months prior to study enrollment&#xD;
&#xD;
          -  Stroke within 6 months prior to study enrollment&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Sexually active men or women of childbearing potential who are unwilling to practice&#xD;
             adequate contraception during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Malik Y Kahook, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rocky Mountain Lions Eye Institute</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <results_first_submitted>March 20, 2017</results_first_submitted>
  <results_first_submitted_qc>December 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 5, 2021</results_first_posted>
  <last_update_submitted>February 16, 2022</last_update_submitted>
  <last_update_submitted_qc>February 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Glaucoma, Neovascular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Aflibercept With Laser</title>
          <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
        </group>
        <group group_id="P2">
          <title>Aflibercept</title>
          <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Aflibercept With Laser</title>
          <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks&#xD;
Aflibercept: Details covered in arm description</description>
        </group>
        <group group_id="B2">
          <title>Aflibercept</title>
          <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.&#xD;
Aflibercept: Details covered in arm description</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="3"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="56.33" spread="5.69"/>
                    <measurement group_id="B2" value="61.5" spread="15.63"/>
                    <measurement group_id="B3" value="59.29" spread="11.86"/>
                  </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="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Adverse Events</title>
        <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the incidence of adverse events</description>
        <time_frame>2 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events</title>
          <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the incidence of adverse events</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="3"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Severity of Adverse Events</title>
        <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the severity of adverse events</description>
        <time_frame>2 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of Adverse Events</title>
          <description>Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the severity of adverse events</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="3"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Abcess left thigh</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asthma</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pneumonia</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vitreous hemorrhage</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worsening cataract non-study eye</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worsening Cataract Study eye</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diabetes Mellitus</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Worsening NVG - non-study eye</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Recurrent BCC</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>progression of gall bladder cancer</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>worsening of arthritis Right knee</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>matastatic cancer of liver</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>shortness of breath</title>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <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>
        <type>Secondary</type>
        <title>Rate and Extent of Resolution of Neovascularization</title>
        <description>Compare between Groups A and B the Rate and extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2.</description>
        <time_frame>1 year</time_frame>
        <population>No data was collected or analyzed for this Outcome Measure</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate and Extent of Resolution of Neovascularization</title>
          <description>Compare between Groups A and B the Rate and extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2.</description>
          <population>No data was collected or analyzed for this Outcome Measure</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intraocular Pressure (mmHg) at Baseline</title>
        <description>Intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
        <time_frame>Baseline</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Intraocular Pressure (mmHg) at Baseline</title>
          <description>Intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Study Eye Mean IOP(mmHg) at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="08" upper_limit="12"/>
                    <measurement group_id="O2" value="23.5" lower_limit="14" upper_limit="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fellow Eye Mean IOP(mmHg) at Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11" lower_limit="08" upper_limit="14"/>
                    <measurement group_id="O2" value="22.75" lower_limit="17" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intraocular Pressure (mmHg) at Week 52</title>
        <description>Mean intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
        <time_frame>Week 52</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Intraocular Pressure (mmHg) at Week 52</title>
          <description>Mean intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Study Eye Mean IOP(mmHg) at W52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="08" upper_limit="12"/>
                    <measurement group_id="O2" value="15.25" lower_limit="13" upper_limit="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fellow Eye Mean IOP(mmHg) at W52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="08" upper_limit="12"/>
                    <measurement group_id="O2" value="14" lower_limit="06" upper_limit="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Losing &gt; 5 Letters on Visual Acuity in Each Group A and Group B</title>
        <description>Comparison between patients, groups A and B, that lost &gt; 5 letters on visual acuity</description>
        <time_frame>Baseline to Week 52</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Losing &gt; 5 Letters on Visual Acuity in Each Group A and Group B</title>
          <description>Comparison between patients, groups A and B, that lost &gt; 5 letters on visual acuity</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients in Each, Group A and Group B, Gaining &gt; 5 Letters on Visual Acuity</title>
        <description>Comparison of patients in each, group A and group B, that gained &gt; 5 letters on visual acuity</description>
        <time_frame>Baseline to Week 52</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients in Each, Group A and Group B, Gaining &gt; 5 Letters on Visual Acuity</title>
          <description>Comparison of patients in each, group A and group B, that gained &gt; 5 letters on visual acuity</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Visual Acuity at Baseline</title>
        <description>Comparison of visual acuity between groups A and B</description>
        <time_frame>Baseline</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Acuity at Baseline</title>
          <description>Comparison of visual acuity between groups A and B</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>Letters</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64" lower_limit="64" upper_limit="64"/>
                    <measurement group_id="O2" value="37.5" lower_limit="0" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Visual Acuity at Week 52</title>
        <description>Comparison of visual acuity at Week 52 between groups A and B</description>
        <time_frame>Week 52</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Acuity at Week 52</title>
          <description>Comparison of visual acuity at Week 52 between groups A and B</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>Letters</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Study Eye Mean W52 Number of ETDRS Letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.5" lower_limit="0" upper_limit="67"/>
                    <measurement group_id="O2" value="62" lower_limit="34" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fellow Eye Mean W52 Number of ETDRS Letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32" lower_limit="0" upper_limit="64"/>
                    <measurement group_id="O2" value="46.75" lower_limit="0" upper_limit="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparison of the Visual Field Between Groups</title>
        <description>Comparison of the Visual field s measured by HVF 24-2 SITA Standards between groups A and B</description>
        <time_frame>1 year</time_frame>
        <population>No data was collected or analyzed for this Outcome Measure during the clinical trial.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Comparison of the Visual Field Between Groups</title>
          <description>Comparison of the Visual field s measured by HVF 24-2 SITA Standards between groups A and B</description>
          <population>No data was collected or analyzed for this Outcome Measure during the clinical trial.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure of the Optical Coherence Tomography(OCT) Outcomes</title>
        <description>Evaluation of the Optical Coherence Tomography(OCT) outcomes (average retinal nerve fiber layer(RNFL) and central macular thickness), Compared between groups A and B.</description>
        <time_frame>Baseline to Week 52</time_frame>
        <population>The database in OCT was corrupted and the data was lost</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks&#xD;
Aflibercept: Details covered in arm description</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.&#xD;
Aflibercept: Details covered in arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Measure of the Optical Coherence Tomography(OCT) Outcomes</title>
          <description>Evaluation of the Optical Coherence Tomography(OCT) outcomes (average retinal nerve fiber layer(RNFL) and central macular thickness), Compared between groups A and B.</description>
          <population>The database in OCT was corrupted and the data was lost</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Need for Surgical Intervention</title>
        <description>Comparison between groups A and B and the need for surgical intervention in both arms during the follow-up period</description>
        <time_frame>1 year</time_frame>
        <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Need for Surgical Intervention</title>
          <description>Comparison between groups A and B and the need for surgical intervention in both arms during the follow-up period</description>
          <population>One participant from group Aflibercept with Laser did not complete analysis due to death. Analysis is limited due to small sample size.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Need for Additional IOP Lowering Medications</title>
        <description>Comparison between groups A and B for the need of additional IOP lowering medications</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Need for Additional IOP Lowering Medications</title>
          <description>Comparison between groups A and B for the need of additional IOP lowering medications</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Extent of Resolution of Neovascularization Between Groups</title>
        <description>Comparison of groups A and B and the extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2</description>
        <time_frame>1 year</time_frame>
        <population>NVG Staging not recorded</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Extent of Resolution of Neovascularization Between Groups</title>
          <description>Comparison of groups A and B and the extent of resolution of neovascularization in patients with NVG Stages 1 &amp; 2</description>
          <population>NVG Staging not recorded</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of the Average Retinal Nerve Fiber Layer (RNFL)</title>
        <description>Comparison between groups A and B of the average retinal nerve fiber layer (RNFL) as measured by Optical Coherence Tomography (OCT)</description>
        <time_frame>1 year</time_frame>
        <population>The OCT database was corrupted and the data was lost</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept With Laser</title>
            <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept</title>
            <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Average Retinal Nerve Fiber Layer (RNFL)</title>
          <description>Comparison between groups A and B of the average retinal nerve fiber layer (RNFL) as measured by Optical Coherence Tomography (OCT)</description>
          <population>The OCT database was corrupted and the data was lost</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Aflibercept With Laser</title>
          <description>A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks</description>
        </group>
        <group group_id="E2">
          <title>Aflibercept</title>
          <description>2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes Mellitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vitreous hemmorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Worsening cataract non-study eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Worsening Cataract Study eye</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Worsening NVG - non-study eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>progression of gall bladder cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>metastatic cancer affecting liver</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>worsening arthritis right knee</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>shortness of breath</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Recurrent BCC</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abcess left thigh</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </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>Rachel Gerle</name_or_title>
      <organization>University of Colorado School of Medicine</organization>
      <phone>720-848-2020</phone>
      <email>rachel.gerle@ucdenver.edu</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/NCT01711879
org study id: 12-1526
nct id: NCT01711879
lead sponsor: 
has dmc: No
This 52 week study will assess the use of intravitreal aflibercept injections in patients
      with neovascular glaucoma (NVG) compared to standard of care panretinal photocoagulation.

      The investigators hypothesize that the neovascularization of the iris and angle present in
      neovascular glaucoma will resolve more quickly in eye treated with intravitreal aflibercept
      injection alone and result in increased comfort and preservation of visual field as compared
      to current standard of care utilizing pan-retinal photocoagulation. The advantages to
      intravitreal aflibercept injection use could include resolution of NVI/NVA
      (neovascularization of the iris/neovascularization of the angle) leading to quicker pain
      relief and quicker lowering of IOP (intraocular pressure).
The two arms of this study will compare current common practice (initial intravitreal
      anti-VEGF (vascular endothelial growth factor) to study treatment (VEGF) injection only) for
      52 weeks.

      This single center study will consist of 20 patients with NVG. Patients will be randomized
      to:

        -  Group A: A single injection of 2mg (0.05ml) intravitreal aflibercept injection at
           baseline followed by standard of care laser with observation for a total of 52 weeks.

      or

        -  Group B: 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two
           additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52
           weeks.

      Clinical assessment will include pain assessment (Universal Pain Scale), best corrected
      visual acuity (ETDRS), ophthalmic examination, anterior segment assessment including number
      of clock-hours of NVI/NVA, gonioscopy, anterior segment photography, visual field test
      (Humphrey SITA- Standard 24-2), optic nerve OCT (Zeiss Cirrus Optic Disc Cube 200x200),
      macular OCT (Cube scan 512 x 128 and 5 Line Raster), fluorescein angiography (initial iris
      phase followed by standard retinal angiography), and concurrent medical/ocular medications.
      Qualitative assessment of neovascularization will be made by the investigator based on
      comparison to baseline angiography.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events
time frame: 2 year
description: Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the incidence of adverse events
measure: Severity of Adverse Events
time frame: 2 year
description: Assess the safety profile of repeated intravitreal aflibercept injections in patients with NVG by evaluating the severity of adverse events
measure: Rate and Extent of Resolution of Neovascularization
time frame: 1 year
description: Compare between Groups A and B the Rate and extent of resolution of neovascularization in patients with NVG Stages 1 & 2.
measure: Intraocular Pressure (mmHg) at Baseline
time frame: Baseline
description: Intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B
measure: Intraocular Pressure (mmHg) at Week 52
time frame: Week 52
description: Mean intraocular pressure(mmHg) as measured by Goldmann applanation tonometry between groups A and B
measure: Number of Patients Losing > 5 Letters on Visual Acuity in Each Group A and Group B
time frame: Baseline to Week 52
description: Comparison between patients, groups A and B, that lost > 5 letters on visual acuity
measure: Number of Patients in Each, Group A and Group B, Gaining > 5 Letters on Visual Acuity
time frame: Baseline to Week 52
description: Comparison of patients in each, group A and group B, that gained > 5 letters on visual acuity
measure: Visual Acuity at Baseline
time frame: Baseline
description: Comparison of visual acuity between groups A and B
measure: Visual Acuity at Week 52
time frame: Week 52
description: Comparison of visual acuity at Week 52 between groups A and B
measure: Comparison of the Visual Field Between Groups
time frame: 1 year
description: Comparison of the Visual field s measured by HVF 24-2 SITA Standards between groups A and B
measure: Measure of the Optical Coherence Tomography(OCT) Outcomes
time frame: Baseline to Week 52
description: Evaluation of the Optical Coherence Tomography(OCT) outcomes (average retinal nerve fiber layer(RNFL) and central macular thickness), Compared between groups A and B.
measure: Number of Patients With Need for Surgical Intervention
time frame: 1 year
description: Comparison between groups A and B and the need for surgical intervention in both arms during the follow-up period
measure: Number of Participants With Need for Additional IOP Lowering Medications
time frame: 1 year
description: Comparison between groups A and B for the need of additional IOP lowering medications
measure: Extent of Resolution of Neovascularization Between Groups
time frame: 1 year
description: Comparison of groups A and B and the extent of resolution of neovascularization in patients with NVG Stages 1 & 2
measure: Evaluation of the Average Retinal Nerve Fiber Layer (RNFL)
time frame: 1 year
description: Comparison between groups A and B of the average retinal nerve fiber layer (RNFL) as measured by Optical Coherence Tomography (OCT)
arm group label: Aflibercept with Laser
arm group type: Active Comparator
description: A single injection of 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by standard of care laser with observation for a total of 52 weeks
arm group label: Aflibercept
arm group type: Experimental
description: 2mg (0.05ml) intravitreal aflibercept injection at baseline followed by two additional injections at 4 weeks and 8 weeks, then every 8 weeks for a total of 52 weeks.
intervention type: Drug
intervention name: Aflibercept
description: Details covered in arm description
arm group label: Aflibercept
arm group label: Aflibercept with Laser
other name: Eylea
criteria: 
gender: All
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: No
last name: Malik Y Kahook, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glaucoma
mesh term: Glaucoma, Neovascular
mesh term: Aflibercept
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 