Clinical trial NCT03246152: Evaluation of the Effect of Intravitreal Injections of Anti-VEGF on Macular Perfusion in Diabetic Patients Using OCTA
Official title: Evaluation of the Effect of Repeated Intravitreal Injections of Anti-VEGF on Macular Perfusion in Diabetic Patients Using Optical Coherence Tomography Angiography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Macular Edema
Ischemic Maculopathy
Keywords: Anti-VEGF safety
Ischemic Maculopathy
Diabetic Macular Edema
OCTA
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2017-08-11
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: FAZ Area Change
timeFrame: At baseline and after 3-6 consecutive monthly injections.
measure: Macular Capillary Density Change at Full Retinal Thickness
timeFrame: At baseline and after 3-6 consecutive monthly injections.
Secondary outcomes:
measure: BCVA Change
timeFrame: At baseline and after 3-6 consecutive monthly injections.
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University Faculty of Medicine
Study officials:
affiliation: Cairo University
name: Khaled E El Rakhawy, PhD
role: STUDY_DIRECTOR
affiliation: Cairo University
name: Karim A Raafat, PhD
role: STUDY_DIRECTOR
affiliation: Cairo University
name: Ahmed AA Abdel Kader, PhD
role: STUDY_CHAIR
affiliation: Cairo University
name: Ayman GA Elnahry, MSc
role: PRINCIPAL_INVESTIGATOR
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