Additional Effect of Subthreshold Micropulse Laser to Intravitreous Injection of Bevacizumab on Diabetic Macular Edema

Additional Effect of Sub-threshold Micro-pulse Laser to Intra-vitreous Injection of Bevacizumab on Diabetic Macular Edema: A Randomized Double-blinded Clinical Trial

In this study, all eyes with diabetic macular edema who meet the inclusion criteria and do not meet the exclusion criteria will be included. After the eye examination, the eyes will be randomly divided into 2 groups {group A: intravitreal interjection of Bevacizumab and subthreshold micropulse laser, and group B: intravitreal injection of Bevacizumab alone}. For both groups, 3 intravitreal injections of bevacizumab with a dose of 1.25 mg will be performed, in sterile conditions at 1-month intervals as a loading dose.

A subthreshold micropulse laser will be performed after the third injection in group A and a sham laser will be performed after the third injection in group B. Then, the intravitreal injection of Bevacizumab will be continued if the central thickness of the macula is equal to or greater than 300 microns.

The follow-up will be performed 2, 3, 4, 6, 8, 10, and 12 months after the first injection. In each follow-up (except for the first month), ophthalmological examinations and Optical Coherence Tomography will be performed.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Combination product: Intravitreal bevacizumab injection with subthreshold micropulse laser; Drug: Intravitreal bevacizumab injection alone

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Ophthalmic Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 18 years diabetic patients
• Center-involved diabetic macular edema
• Mean central subfield thickness >300 micrometers
• Best-corrected visual acuity between 20/40 and 20/400

Exclusion Criteria:

• hemoglobin A1c > 8
• High-risk proliferative diabetic retinopathy
• Prior treatment with intravitreal or peribulbar injections within the preceding 3 months
• History of panretinal photocoagulation within the former 4 months
• History of macular photocoagulation
• Hx of Intraocular surgery (except cataract extraction)
• cataract extraction less than 6 months ago
• Macular edema due to a cause other than diabetic retinopathy
• Any other ocular condition that visual acuity would not improve from the resolution of the edema (eg, foveal atrophy)
• Substantial cataract estimated to have reduced visual acuity by >3 lines
• uveitis, neovascular glaucoma, exudative age-related macular degeneration, high risk proliferative diabetic retinopathy
• vitreomacular traction or epiretinal membrane
• uncontrolled glaucoma ( > 30 millimeters of mercury with anti-glaucoma medications)
• Not having: Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simultaneous intravitreal bevacizumab injection with subthreshold micropulse laser; After the eye examination, the eyes will be randomly divided into 2 groups {group A: intravitreal interjection of Bevacizumab and subthreshold micropulse laser, and group B: intravitreal injection of Bevacizumab alone}. For both groups, 3 intravitreal injections of bevacizumab with a dose of 1.25 mg will be performed, in sterile conditions at 1-month intervals as a loading dose. A subthreshold micropulse laser will be performed after the third injection in group A. Then, the intravitreal injection of Bevacizumab will be continued if the central thickness of the macula is equal to or greater than 300 microns. The follow-up will be performed 2, 3, 4, 6, 8, 10, and 12 months after the first injection. In each follow-up (except for the first month), ophthalmological examinations and Optical Coherence Tomography will be performed.	Combination product: Intravitreal bevacizumab injection with subthreshold micropulse laser; Group A: intravitreal interjection of Bevacizumab and subthreshold micropulse laser
Active Comparator: Intravitreal bevacizumab injection alone; After the eye examination, the eyes will be randomly divided into 2 groups {group A: intravitreal interjection of Bevacizumab and subthreshold micropulse laser, and group B: intravitreal injection of Bevacizumab alone}. For both groups, 3 intravitreal injections of bevacizumab with a dose of 1.25 mg will be performed, in sterile conditions at 1-month intervals as a loading dose. A sham laser will be performed after the third injection in group B. Then, the intravitreal injection of Bevacizumab will be continued if the central thickness of the macula is equal to or greater than 300 microns. The follow-up will be performed 2, 3, 4, 6, 8, 10, and 12 months after the first injection. In each follow-up (except for the first month), ophthalmological examinations and Optical Coherence Tomography will be performed.	Drug: Intravitreal bevacizumab injection alone; Group B: Intravitreal injection of Bevacizumab alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline central macular thickness at 2 months	Change from baseline central macular thickness at 2 months using Optical Coherence Tomography	Change from baseline to 2 months
Change from 2 months central macular thickness at 3 months	Change from 2 months central macular thickness at 3 months using Optical Coherence Tomography	Change from 2 months to 3 months
Change from 3 months central macular thickness at 4 months	Change from 3 months central macular thickness at 4 months using Optical Coherence Tomography	Change from 3 months to 4 months
Change from 4 months central macular thickness at 6 months	Change from 4 months central macular thickness at 6 months using Optical Coherence Tomography	Change from 4 months to 6 months
Change from 6 months central macular thickness at 8 months	Change from 6 months central macular thickness at 8 months using Optical Coherence Tomography	Change from 6 months to 8 months
Change from 8 months central macular thickness at 10 months	Change from 8 months central macular thickness at 10 months using Optical Coherence Tomography	Change from 8 months to 10 months
Change from 10 months central macular thickness at 12 months	Change from 10 months central macular thickness at 12 months using Optical Coherence Tomography	Change from 10 months to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline visual acuity at 2 months	Change from baseline best-corrected visual acuity at 2 months	Change from baseline to 2 months
Change from 2 months visual acuity at 3 months	Change from 2 months best-corrected visual acuity at 3 months	Change from 2 months to 3 months
Change from 3 months visual acuity at 4 months	Change from 3 months best-corrected visual acuity at 4 months	Change from 3 months to 4 months
Change from 4 months visual acuity at 6 months	Change from 4 months best-corrected visual acuity at 6 months	Change from 4 months to 6 months
Change from 6 months visual acuity at 8 months	Change from 6 months best-corrected visual acuity at 8 month	Change from 6 months to 8 months
Change from 8 months visual acuity at 10 months	Change from 8 months best-corrected visual acuity at 10 months	Change from 8 months to 10 months
Change from 10 months visual acuity at 12 months	Change from 10 months best-corrected visual acuity at 12 months	Change from 10 months to 12 months

Collaborators and Investigators

• Sponsor: Shahid Beheshti University of Medical Sciences
• Investigators: Principal Investigator: Alireza Ramezani, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Anticipated): October 15, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: September 10, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 14016 (company internal)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No