Clincosm LogoSign in Get a demo

IMPACT: Evaluation of the Effect of Intravitreal Injections of Anti-VEGF on Macular Perfusion in Diabetic Patients Using OCTA

Sponsor
Cairo University (Other)
Overall Status
Completed
CT.gov ID
NCT03246152
Collaborator
(none)
31
Enrollment
1
Location
1
Arm
14
Actual Duration (Months)
2.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Anti-vascular endothelial growth factor (VEGF) drugs are the mainstay of therapy for diabetic macular edema (DME), substantially improving visual acuity for many diabetics worldwide, and proving effective for treatment of both non-proliferative and proliferative diabetic retinopathy.

Many studies such as Diabetic Retinopathy Clinical Research Network studies, RESTORE Study, and The BOLT Study have supported the use of different anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments.

Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract and retinal detachment. The effect of anti-VEGF drugs on macular perfusion has been inconclusive, with mixed reports of increase, decrease or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischaemic retinas were not included. Retinal ischemia is an important factor in the progression and prognosis of diabetic retinopathy.

Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the studies. Despite its clinical usefulness, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) is a new noninvasive method of acquiring high-resolution images of the retinal vasculature that can be utilized in the treatment of retinal disease without the need for dye injection. It allows the visualization of the superficial and deep retinal capillary layers separately and the construction of microvascular flow maps.

Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics.

In this study, investigators aim to evaluate the effect of repeated intravitreal injections of different Anti-VEGF agents on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

This is a prospective interventional study to evaluate the effect of repeated intravitreal injections of Anti-VEGF on macular perfusion in diabetic patients using optical coherence tomography angiography (OCTA).

Each patient will receive a detailed ophthalmologic examination including measurement of BCVA as well as applanation tonometry, undilated and dilated slit-lamp biomicroscopic examination and indirect fundus examination.

Duration of diabetes and its control through HbA1C measurement will be recorded for each patient.

Type 1 and 2 diabetic patients found to have BCVA worse than 6/6 and clinical evidence of macular edema will undergo SD OCT and FA.

Patients with center involved macula edema detected by SD OCT will be included in the study and will undergo baseline macular OCTA.

These patients will then undergo intravitreal injections of Anti-VEGF monthly for 3 months then OCTA will be repeated to evaluate changes in macular perfusion and SD OCT will be repeated to assess retinal thickness. Patients with center involving macular edema on SD-OCT after the first 3 injections will continue to receive intravitreal Anti-VEGF injections monthly until the edema subsides or the study duration ends. These patients then undergo a final macular OCTA for perfusion evaluation and SD OCT for thickness assessment.

OCTA will be performed with an Avanti RTVue XR system (Optovue, Inc., Fremont, CA, USA). Area of FAZ and capillary density at each capillary layer will be calculated before and after interventions using the OCTA machine software and ImageJ software.

All statistical analyses will be done using IBM SPSS v20.0 statistical software (IBM Corporation, NY, USA). Descriptive statistics will be calculated, and the data will be summarized as mean ± SD for numerical data, and as frequencies and percentages for categorical data.

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Evaluation of the Effect of Repeated Intravitreal Injections of Anti-VEGF on Macular Perfusion in Diabetic Patients Using Optical Coherence Tomography Angiography
Actual Study Start Date :
Oct 23, 2017
Actual Primary Completion Date :
Dec 24, 2018
Actual Study Completion Date :
Dec 24, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Bevacizumab group

Monthly intravitreal injection of 2.5 mg of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema.

Drug: Bevacizumab
Repeated intravitreal injections of Bevacizumab monthly
Other Names:
  • Avastin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. FAZ Area Change [At baseline and after 3-6 consecutive monthly injections.]

      Effect of repeated intravitreal Anti-VEGF injections on Foveal Avascular Zone (FAZ) area measured using the freehand tool of ImageJ

    2. Macular Capillary Density Change at Full Retinal Thickness [At baseline and after 3-6 consecutive monthly injections.]

      Effect of repeated intravitreal Anti-VEGF injections on macular capillary density using the change in the skeletonized vascular density and fractal dimension measured by ImageJ

    Secondary Outcome Measures

    1. BCVA Change [At baseline and after 3-6 consecutive monthly injections.]

      Correlation of BCVA change with degree of capillary non-perfusion before and after injections

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients ≥ 18 years old

    2. Type 1 or 2 diabetes mellitus

    3. Decreased BCVA due to diabetic macular edema

    4. Center involvement by the edema on spectral domain optical coherence tomography (SD OCT)

    5. Any stage of diabetic retinopathy

    Exclusion Criteria:

    1. Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.)

    2. History of vitreoretinal surgeries (excluding intravitreal injections)

    3. Any previous treatment for diabetic macular edema

    4. Presence of epiretinal membrane involving the macula or vitreomacular traction

    5. Media opacity preventing good image quality

    6. Uncontrolled glaucoma

    7. Thromboembolic events within 6 months

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cairo University Faculty of Medicine Cairo Egypt

    Sponsors and Collaborators

    • Cairo University

    Investigators

    • Study Director: Khaled E El Rakhawy, PhD, Cairo University
    • Study Director: Karim A Raafat, PhD, Cairo University
    • Study Chair: Ahmed AA Abdel Kader, PhD, Cairo University
    • Principal Investigator: Ayman GA Elnahry, MSc, Cairo University

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Ayman Gehad Elnahry, Clinical Demonstrator, Cairo University
    ClinicalTrials.gov Identifier:
    NCT03246152
    Other Study ID Numbers:
    • N-79-2017
    First Posted:
    Aug 11, 2017
    Last Update Posted:
    Jan 30, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Ayman Gehad Elnahry, Clinical Demonstrator, Cairo University
    Anti-VEGF safety
    Ischemic Maculopathy
    Diabetic Macular Edema
    OCTA
    Additional relevant MeSH terms:
    Macular Edema
    Macular Degeneration
    Bevacizumab

    Study Results

    Participant Flow

    Recruitment Details This is the number of enrolled patients that completed the study.
    Pre-assignment Detail
    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    Period Title: Overall Study
    STARTED 31
    COMPLETED 28
    NOT COMPLETED 3

    Baseline Characteristics

    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    Overall Participants 31
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    28
    90.3%
    >=65 years
    3
    9.7%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    54.8
    (6.5)
    Sex: Female, Male (Count of Participants)
    Female
    17
    54.8%
    Male
    14
    45.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    0
    0%
    More than one race
    0
    0%
    Unknown or Not Reported
    31
    100%
    Region of Enrollment (participants) [Number]
    Egypt
    31
    100%

    Outcome Measures

    1. Primary Outcome
    Title FAZ Area Change
    Description Effect of repeated intravitreal Anti-VEGF injections on Foveal Avascular Zone (FAZ) area measured using the freehand tool of ImageJ
    Time Frame At baseline and after 3-6 consecutive monthly injections.

    Outcome Measure Data

    Analysis Population Description
    Patients with adequate image quality
    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    Measure Participants 26
    Mean (Standard Deviation) [mm^2]
    0.03
    (0.1)
    2. Primary Outcome
    Title Macular Capillary Density Change at Full Retinal Thickness
    Description Effect of repeated intravitreal Anti-VEGF injections on macular capillary density using the change in the skeletonized vascular density and fractal dimension measured by ImageJ
    Time Frame At baseline and after 3-6 consecutive monthly injections.

    Outcome Measure Data

    Analysis Population Description
    Patients with adequate image quality
    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    Measure Participants 26
    Mean (Standard Deviation) [percentage of vascularity]
    -2.5
    (5.72)
    3. Secondary Outcome
    Title BCVA Change
    Description Correlation of BCVA change with degree of capillary non-perfusion before and after injections
    Time Frame At baseline and after 3-6 consecutive monthly injections.

    Outcome Measure Data

    Analysis Population Description
    Patients with good image quality
    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    Measure Participants 26
    Mean (Standard Deviation) [Logmar]
    -0.21
    (0.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bevacizumab Group
    Comments Correlation between change in BCVA and the pre treatment, post treatment, and change in vascular density following 3-6 injections was performed.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Pearson's correlation coefficient
    Comments

    Adverse Events

    Time Frame 3 months
    Adverse Event Reporting Description
    Arm/Group Title Bevacizumab Group
    Arm/Group Description Monthly intravitreal injection of Bevacizumab for at least 3 consecutive months. This is followed by treat and extend regimen after resolution of macular edema. Bevacizumab: Repeated intravitreal injections of Bevacizumab monthly
    All Cause Mortality
    Bevacizumab Group
    Affected / at Risk (%) # Events
    Total 0/31 (0%)
    Serious Adverse Events
    Bevacizumab Group
    Affected / at Risk (%) # Events
    Total 0/31 (0%)
    Other (Not Including Serious) Adverse Events
    Bevacizumab Group
    Affected / at Risk (%) # Events
    Total 18/31 (58.1%)
    Eye disorders
    Subconjunctival hemorrhage 13/31 (41.9%)
    Ocular irritation 5/31 (16.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title Dr. Ayman Elnahry
    Organization Cairo University
    Phone 00201224927604
    Email ayman_elnahri@hotmail.com
    Responsible Party:
    Ayman Gehad Elnahry, Clinical Demonstrator, Cairo University
    ClinicalTrials.gov Identifier:
    NCT03246152
    Other Study ID Numbers:
    • N-79-2017
    First Posted:
    Aug 11, 2017
    Last Update Posted:
    Jan 30, 2020
    Last Verified:
    Jan 1, 2020