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

Study Overview
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Brief Summary
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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.

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

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Combination Product: Intravitreal bevacizumab injection with subthreshold micropulse laser
* Drug: Intravitreal bevacizumab injection alone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simultaneous intravitreal bevacizumab injection with subthreshold micropulse laser<br>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<br>* Group A: intravitreal interjection of Bevacizumab and subthreshold micropulse laser<br>|
| Active Comparator: Intravitreal bevacizumab injection alone<br>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<br>* Group B: Intravitreal injection of Bevacizumab alone<br>|

What is the study measuring?
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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 |