Imaging Parameters and DME Treatment Response

Imaging Parameters Predicting Treatment Response in Patients With Diabetic Macular Edema

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. While anti-VEGF treatments and to a lesser extent corticosteroid and macular photocoagulation have improved outcomes in patients with DME, no single therapy is universally effective and currently there is no a priori means of determine which patients will respond best to any given therapy. The purpose of this study is to determine whether specific parameters of ocular imaging studies including optical coherence tomography and fluorescein angiography can predict response to treatment in patients with DME. This is a prospective observational cohort study that will collect clinical data and imaging studies obtained as standard of care. Up to 150 subjects with clinically significant DME will be enrolled at Duke Eye Center or its satellite offices. These imaging studies will be analyzed to determine whether specific parameters are associated with poor or favorable response to specific treatments. There will be no intervention as part of this observational trial, thus the primary risk to subjects is loss of confidentiality, which will be minimized by the study team.

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy; Diabetic Macular Edema
• Intervention / Treatment: Other: No intervention

Detailed Description

The investigators hypothesize that DME is a common endpoint caused by differing pathobiology which varies between patients. Clinically fluorescein angiography (FA) and optical coherence tomography (OCT) are used to diagnose and assess diabetic retinopathy including DME. These two imaging modalities provide different biological information with FA giving functional data regarding the perfusion and integrity of the retinal water homeostasis system where OCT gives structural information including the quantity and location of fluid in patients with DME. The investigators believe that careful analysis of both the leakage pattern on FA and the characteristics of intraretinal fluid on OCT have potential to provide insight into the predominant mechanism of DME in an individual patient. Specifically, it has been proposed that at least two forms of DME exist, focal and diffuse. In focal DME, leakage seen on FA originates predominantly from leaking microaneurysms present in the retinal microvasculature, which are markers for endothelial dysfunction and focal breakdown of the blood retinal barrier. Similarly, it has been hypothesized that focal leakage imaged by OCT will result in accumulation of noncystic fluid in the extracellular space. In contrast, diffuse pattern leakage has no discernable source on FA and it is believed that this pattern represents failure of the Müller and RPE cell pump function resulting in accumulation of intracellular fluid in the retina. Diffuse leakage imaged with OCT may appear as cystic fluid accumulation which represents swollen Müller or other retinal cells.

In clinical practice, most patients with DME have a mixture of focal and diffuse leakage with one type being predominant. The investigators hypothesize that, because they are driven by disparate pathobiology, different DME subtypes will respond differently to treatment. Thus, it may be possible to use fluorescein angiography and/or optical coherence tomography to predict the optimal treatment for an individual patient, thereby improving patient outcomes and possibly reducing treatment burden. To date, there are no prospective studies correlating FA and OCT imaging parameters with response to specific therapies, nor is there prospective data on using imaging parameters to guide choice of treatment modality in subjects with DME. As a first step toward determining whether imaging parameters predict treatment response, the investigators will prospectively collect imaging, treatment and outcome data in patients with diabetic macular edema treated at Duke Eye Center.

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

• Study Contact: Name: Michael Allingham, MD, PhD; Phone Number: 919-684-8111; Email: mike.allingham@dm.duke.edu
• Study Contact Backup: Name: Priyatham Mettu, MD; Phone Number: 919-684-9010

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of DME in one or both eyes which is visually significant in the opinion of the clinician/investigator.

Description

Inclusion Criteria:

• Able to provide written informed consent
• Diagnosis of DME in one or both eyes which is visually significant in the opinion of the clinician.

Exclusion Criteria:

• Macular edema secondary to causes other than diabetes
• Known or suspected sensitivity or allergy to fluorescein dye
• Significant media opacity (e.g. cataract or vitreous hemorrhage)
• Prior history of vetrectomy surgery

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Diabetic Macular Edema; Patients with Diabetic Macular Edema. There will be no intervention in this cohort, only observation of standard of care.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in disease state characteristics in response to therapy	Generated software will be used to analyze FA and OCT images at the start, duration and end of the study. We have developed automated segmentation software for both optical coherence tomography (OCT) and fluorescein angiography (FA). This software will be used to quantify specific imaging parameters including leakage area, diffuse leakage, focal leakage from FA and cyst volume, cyst location, inner retinal volume and outer retinal volume from OCT.	Six months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in visual acuity using ETDRS visual acuity assessment	Visual acuity will be assessed using ETDRS visual acuity charts.	Baseline, Six months post treatment

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Michael Allingham, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: diabetic macular edema; diabetic retinopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Macular Edema; Edema
• Other Study ID Numbers: Pro00061249

Drug and device information, study documents

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