Treatment of Diabetic Macular Edema With Aflibercept and Micropulse Laser

Study Overview
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Brief Summary
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The goal of this pilot study is to investigate the safety and efficacy of micropulse (MP) macular laser in combination with intravitreal aflibercept for the treatment of centre-involved diabetic macular edema.

Detailed Description
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Diabetic macular edema (DME) is one of the major causes of visual decline among diabetic patients. Early Treatment of Diabetic Retinopathy Study has established focal/grid macular laser as the standard of treatment for clinically significant macular edema. More recently, intravitreal injections of anti-VEGF agents, either as monotherapy or in combination with focal/grid laser, have proven to be superior for the treatment of DME compared to laser alone. Micropulse (MP) macular laser involves applying the laser in a fraction of the time within very small pockets of energy. Unline traditional focal/grid macular laser, the micropulse method of delivery does not leave any visible burns on the retina. A recent release by the Diabetic Retinopathy Clinical Research Network has shown that deferring focal/grid laser and treating diabetic macular edema with only anti-VEGF may lead to better visual outcomes. Since MP laser does not have the undesired side effect of leaving laser scars on the macula, the study is to show that prompt MP laser in addition to anti-vegf injections may lead to better visual outcomes and/or decreased treatment burden without the undesired side effect of macular scarring.

Official Title
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Treatment of Diabetic Macular Edema With Aflibercept and Micropulse Laser

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Combination Product: Micropulse Laser
* Device: Sham Laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type I or Type II Diabetes Mellitus Presence of centre-involved Diabetic Macular Edema (DME) with the Central Macular Thickness (CMT) of ≥ 310µm on the spectral-domain Optical Coherence Tomography (OCT) Best corrected Visual Acuity (BCVA) between, and including, 20/30 and 20/400 in the study eye. Patient's willingness and ability to attend the study visits Exclusion Criteria: Any other potential causes of macular edema such as active uveitis, epiretinal membrane, post-operative CME, and vitromacular traction Any history of major intraocular surgery (such as cataract surgery or vitrectomy) in the study eye within prior six months, or anticipated need for intraocular surgery within the next six months from the enrollment Any major ocular pathology limiting potential vision such as large macular scars, vitreous hemorrhage, corneal opacities, visually significant cataracts, advanced glaucoma, or other types of optic neuropathy Any history of Panretinal Photocoagulation (PRP) in the study eye or anticipated need for PRP within the next 6 months from enrollment Any history of DME treatment (focal laser, anti-VEGF, or intraocular/periocular steroids) in the study eye in the past 4 months prior to the enrollment Significant renal disease requiring dialysis Significant heart disease, stroke or transient ischemic attack requiring hospitalization in the past 4 months prior to the study Presence of active ocular or periocular infection Presence of active intraocular inflammation Known hypersensitivity to aflibercept or to any ingredient in the formulation or to any component of the container

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: This will be a parallel study comparing the results of patients who receive aflibercept and micropulse laser versus those who only receive aflibercept. The second group will receive sham laser to prevent placebo effects.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aflibercept with Micropulse Laser<br>Aflibercept 2mg (0.05mL) injected intravitreally every 4 weeks or as needed Micropulse Laser at initial visit and reassessed every 12 weeks. | Combination Product: Micropulse Laser<br>* Aflibercept injection with Micropulse laser.<br>|
| Sham Comparator: Aflibercept with Sham Laser<br>Aflibercept 2mg (0.05mL) injected intravitreally every 4 weeks or as needed Sham Laser at initial visit and reassessed every 12 weeks. | Device: Sham Laser<br>* Aflibercept injection with Sham Laser<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of injections for each group | Number of intravitreal injections for each group | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in visual acuity | Changes in visual acuity from baseline to 24 adjusted for baseline | 24 weeks | 
| Changes in visual acuity | Changes in visual acuity from baseline to 48 weeks adjusted for baseline | 48 weeks | 
| Changes in OCT Central Macular Thickness and Volume | Measurement changes in central macular thickness at 24 weeks | 24 weeks | 
| Changes in OCT Central Macular Thickness and Volume | Measurement changes in central macular thickness at 48 weeks | 48 weeks | 
| Number of injections half way | Number of intravitreal injections of each group at 24 weeks | 24 weeks | 
| Proportion of eyes with 2 or 3 lines of visual gain or loss | Improvement or deterioration of vision of 2 or 3 lines at 24 weeks | 24 weeks | 
| Proportion of eyes with 2 or 3 lines of visual gain or loss | Improvement or deterioration of vision of 2 or 3 lines at 48 weeks | 48 weeks | 
| Proportion of eyes that achieve 20/20 vision | Eyes that are able to see 20/20 at 24 weeks regardless of baseline | 24 weeks | 
| Proportion of eyes that achieve 20/20 vision | Eyes that are able to see 20/20 at 48 weeks regardless of baseline | 48 weeks | 
| Proportion of eyes that have PRP, vitreous hemorrhage, and vitrectomy. | Proportion of eyes in each study group that require panretinal photocoagulation, have a vitreous hemorrhage, or require a vitrectomy during the course of the study. | 48 weeks | 
| Proportion of eyes that had vision or OCT improvement | In patients with HbA1c ≤ 8% or separately measured in patients with HbA1C > 8% | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DME, Micropulse Laser, Anti-VEGF