Treatment of Diabetic Macular Edema With Aflibercept and Micropulse Laser (DAM)

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Combination product: Micropulse Laser; Device: Sham Laser

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L4X 2Z9
      • Mississauga Retina Institute
    • Toronto, Ontario, Canada, M3C 0G9
      • Toronto Retina Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Aflibercept with Micropulse Laser; 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; Aflibercept injection with Micropulse laser.
Sham Comparator: Aflibercept with Sham Laser; 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; Aflibercept injection with Sham Laser

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Keyvan Koushan
• Investigators: Principal Investigator: Keyvan Koushan, MD, FRCSC, Toronto Retina Institute

Publications and helpful links

General Publications

• Koushan K, Eshtiaghi A, Fung P, Berger AR, Chow DR. Treatment of Diabetic Macular Edema with Aflibercept and Micropulse Laser (DAM Study). Clin Ophthalmol. 2022 Apr 8;16:1109-1115. doi: 10.2147/OPTH.S360869. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): May 9, 2019
• Study Completion (Actual): May 9, 2019

Study Registration Dates

• First Submitted: May 1, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 8, 2017

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: DME, Micropulse Laser, Anti-VEGF
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: 19228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The results of this study will be analyzed statistically which will be shared with other members of the scientific community but the individual participant data along with their identifiers will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No