Objective
The primary goal of these studies is to better understand the cause and progression of eye disease in people with diabetes by evaluating a broad range of disease severity in eyes with and without diabetic macular edema. Other goals include evaluating how imaging and other ocular testing changes with increasing severity of diabetic retinal disease. This study may also help in the future to develop new measures that can be used to research new treatments for diabetic eye diseases.
Background Rationale
One of the major hurdles to the development of novel, more effective therapies for diabetic retinal disease (DRD) is the limited number of primary endpoints available for use in regulatory trials. The current endpoints require long trial durations and large numbers of participants to show efficacy. A greater understanding of the structural and functional changes in the retina that occur in people with diabetes is needed to develop or validate new endpoints that could lead to new therapeutic targets and to evaluate the effects of interventions aimed at stopping or slowing the progression of DRD. Recent advances in imaging and technology provide the ability to characterize more fully progressive changes in the retina and to measure several different components of visual function. The first step in meeting this need is to administer state-of-the art imaging and functional testing to patients with diabetes, ranging from those who are newly diagnosed with no apparent retinal disease to those with advanced disease or diabetic macular edema warranting treatment.
Description of Project
Despite improved glycemic and systemic control for many patients over the past several decades, diabetic retinopathy (DR) develops and progresses in a large proportion of patients with diabetes, and visual loss from diabetic complications continues to be a leading cause of blindness in the U.S. and other developed countries worldwide. Although the availability of effective treatments for DR and diabetic macular edema (DME) exist, many obstacles must be overcome to obtain these treatment benefits. Additionally, the costs for care are substantial, and each treatment carries the risk of serious complications.
A major hurdle to the development of novel, more effective therapies for diabetic retinal disease (DRD) is the limited number of primary endpoints available for use in regulatory trials that are required for approval of new therapies for DRD. The current US Food and Drug Administration-approved endpoints necessitate long trial durations and large numbers of participants to show efficacy. A greater understanding of the structural and functional changes in the retina that occur in people with diabetes is needed to develop primary endpoints as well as validate surrogate and clinical endpoints that could lead to new therapeutic targets and to evaluate the effects of interventions aimed at stopping or slowing the progression of DRD. Recent advances in imaging and technology provide the ability to characterize more fully progressive changes in the retina and measure several different components of visual function. The first step in meeting this need is to administer state-of-the-art imaging and functional testing to patients with diabetes, ranging from those who are newly diagnosed without apparent retinopathy to those with advanced retinopathy or diabetic macular edema warranting treatment.
Worldwide, more than 21 million people are affected by DME, and approximately one out of every 14 individuals with diabetes have some degree of DME. In the U.S., at least 5 million people over the age of 40 are estimated to have DR, 899,000 are faced with vision-threatening retinopathy, and an additional 800,000 have DME. This study can provide vital information on the natural progression of DRD and on treatment response in eyes receiving anti-VEGF treatment for DME, aiding in the validation of additional primary surrogate or clinical endpoints to assess future therapies and provide new indications for treatment that might optimize visual outcomes in patients with diabetes.
Anticipated Outcome
This DRCR Retina Network, in collaboration with the Mary Tyler Moore Vision Initiative (MTM Vision) study, will define the ocular structural and functional characteristics of people with diabetes, covering a broad range of diabetes duration and disease severity using standard testing procedures (e.g., retinal photographs, and retinal thickness measurements) as well as three new and innovative functional testing procedures (i.e., AST Manifold quick contrast sensitivity function [qCSF], Konan Medical objective field analyzer [OFA], and LKC Technologies RETEval ERG). The DRCR Retina Network has designed, implemented, and reported results from 32 successful multi-center clinical trials over the last 20 years, many of which have been instrumental in setting the current standards of care for diabetic eye disease. As such, we anticipate that these studies will be similarly enrolled and conducted efficiently and effectively, with focused effort on study participant retention throughout the scheduled follow-up.
Relevance to T1D
Despite improved control of blood sugar, high blood pressure, and blood cholesterol levels for many patients over the past several decades, individuals with type 1 diabetes mellitus (DM) are at increased risk for vision loss from diabetic retinopathy (DR). Previous studies have demonstrated that the vast majority of patients with type 1 diabetes will develop DR over several decades of diabetes duration. One study found that worse blood sugar control and diabetes duration longer than 10 years were associated with approximately 1.5- and 8.5-fold increased odds of central retinal swelling that is a common cause of vision loss in patients with diabetes. The goal of this study is to gain a better understanding of the structural and functional changes that the eyes of patients with diabetes undergo, either over the natural history of diseases or while receiving treatment for diabetic macular edema. This research will provide valuable information about potential endpoints for regulatory trials evaluating future therapies and may provide new predictive markers of DR and DME worsening and response to treatment that may optimize visual outcomes in patients with type 1 DM.