Macular Perfusion Changes After Anti-VEGF Versus Targeted Retinal Photocoagulation in Proliferative Diabetic Retinopathy

NCT04674254 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: MD-39-2021
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM), while proliferative diabetic retinopathy (PDR) is the principal cause of severe visual loss in patients with diabetes. Since 1981, Panretinal photocoagulation (PRP) has been a standard of treatment for PDR. However, PRP can be associated with adverse effects, including visual field constriction, decreased night vision, and worsening of coexisting diabetic macular edema (DME). For this reason, some authors have advocated targeted treatment with PRP. Targeted retinal laser photocoagulation (TRP) is designed to treat areas of retinal capillary non-perfusion and intermediate retinal ischemic zones in PDR that may spare better-perfused tissue from laser-induced tissue scarring. Protocol S by Diabetic Retinopathy Clinical Research Network (DRCR.net) has shown that patients that receive ranibizumab as anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred PRP are non-inferior regarding improving in visual acuity to those eyes receiving standard prompt PRP therapy for the treatment of PDR. Retinal ischemia is an important factor in the progression and prognosis of diabetic retinopathy. Regarding the effect of anti-VEGF drugs on macular perfusion, several studies have shown mixed results with an increase, decrease, or no effect on perfusion in response to anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Fluorescein angiography (FA) was the method used to assess changes in macular perfusion after anti-VEGF injections in most of the clinical trials. Despite its clinical usefulness, however, FA is known to have documented risks. Optical coherence tomography angiography (OCTA) in macular perfusion evaluation in these cases was recommended by some investigators. Several studies have proved the reliability of OCTA in detecting and quantifying macular ischemia in diabetics. The investigators aim to compare changes in the macular perfusion in patients with PDR after treatment with anti-VEGF therapy versus TRP versus Standard PRP using OCTA.

Conditions

Proliferative Diabetic Retinopathy; Vascular Endothelial Growth Factor Overexpression; Diabetic Retinopathy

Keywords

Proliferative diabetic retinopathy; anti-vascular endothelial growth factor; optical coherence tomography angiography; macular perfusion; pan-retinal photocoagulation; fluorescein angiography; visual field

Outcome Measures

Primary Outcomes (2)

• Change in foveal avascular zone area

  The change in the foveal avascular zone area will be compared between the different treatment arms as a measure of macular perfusion change.

  0, 3, 6, 9, and 12 months

• Change in vascular density of the retinal capillary plexuses

  The change in retinal capillary vascular densities at different capillary layers will be compared between the different treatment arms as a measure of macular perfusion change.

  0, 3, 6, 9, and 12 months

Secondary Outcomes (5)

• Change in neovessels

  0, 3, 6, 9, and 12 months

• Change in central macular thickness

  0, 3, 6, 9, and 12 months

• Change in best corrected visual acuity

  0, 3, 6, 9, and 12 months

• Change in macular sensitivity

  0, 3, 6, 9, and 12 months

• Change in orbital blood flow

  0, 3, 6, 9, and 12 months

Study Arms (3)

Anti-vascular endothelial growth factor agent

ACTIVE COMPARATOR

Intravitreal injections of 1.25 mg/0.05 ml of Bevacizumab every 4 weeks through 12- week visit then pro re nata to complete 12 months according to Protocol S.

Drug: Bevacizumab Injection

Targeted retinal photocoagulation

ACTIVE COMPARATOR

Targeted retinal photocoagulation guided by fundus fluorescein angiography will be administered after topical anesthesia, directed to areas of nonperfused peripheral retina plus a 1-disc area margin using the Mainster lens. Subsequent treatments if needed will be delivered at 3 monthly intervals for a minimum follow-up of 12 months. The extent of the laser applied will be determined based on areas of nonperfusion identified by fundus fluorescein angiography.

Procedure: Targeted retinal photocoagulation

Standard pan-retinal photocoagulation

ACTIVE COMPARATOR

Standard pan-retinal photocoagulation will be performed at baseline and then every 3 months thereafter if needed, for a minimum follow-up period of 12 months. PRP will be performed at two consecutive sessions with adherence to the guidelines of the Early Treatment Diabetic Retinopathy Study Group. Following topical anesthesia, 1000 to 1200 laser spots will be applied to the retina at each session with a 532 nm frequency doubled Nd-YAG laser (VISULAS, Carl Zeiss, Germany) using a spot size of 300-500 μm. PRP will be applied in all 4 retina quadrants. The Mainster lens will be used. Retreatment will be done according to the Diabetic Retinopathy Clinical Research network protocol S classification for patients with stable, worsening, or with failure of regression of neovascularization.

Procedure: Standard pan-retinal photocoagulation

Interventions

Bevacizumab Injection DRUG

Bevacizumab will be intravitreally injected every 4 weeks through 12 weeks then pro re nata thereafter for 12 months.

Also known as: Avastin

Anti-vascular endothelial growth factor agent

Targeted retinal photocoagulation PROCEDURE

Targeted retinal photocoagulation will be administered to nonperfused areas detected on fundus fluorescein angiography at baseline and repeated every 3 months as needed for 12 months.

Targeted retinal photocoagulation

Standard pan-retinal photocoagulation PROCEDURE

Standard pan-retinal photocoagulation will be applied to perfused and nonperfused areas of the retinal periphery at baseline and every 3 months as needed for 12 months.

Standard pan-retinal photocoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old
• Type 1 or 2 diabetes mellitus
• PDR
• Central macular thickness less than 300 µm

You may not qualify if:

• Central macular thickness more than 300 µm
• Previous retinal laser treatment
• Ocular conditions that may affect macular perfusion (e.g. retinal vein occlusion, uveitis, vasculitis etc.)
• Any previous treatment for diabetic macular edema.
• Presence of epiretinal membrane involving the macula or vitreomacular traction
• Media opacity such vitreous hemorrhage and dense cataract.
• Patients with previous cataract surgery within the last 3 months.
• Uncontrolled glaucoma
• Thromboembolic events within 6 months
• Tractional retinal detachment.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Faculty of Medicine, Cairo University

Giza, 11956, Egypt

Location

Related Publications (21)

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MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mohamed A Eldaly, MD, PhD

  Cairo University

  STUDY CHAIR

• Ayman G Elnahry, MD, PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Wael A Yussuf, MD, MSc

  Cairo University

  STUDY DIRECTOR

• Ahmed A Abdel-Kader, MD, PhD

  Cairo University

  STUDY DIRECTOR

• Ahmed A Mohalhal, MD, PhD

  Cairo University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Ophthalmology

Study Record Dates

• First Submitted: December 6, 2020
• First Posted: December 19, 2020
• Study Start: March 30, 2021
• Primary Completion: March 15, 2023
• Study Completion: March 15, 2023
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)