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. Current approved endpoints necessitate long trial durations and large numbers of participants to show efficacy. A better understanding of the structural and functional changes that occur in the diabetic retina is needed to develop new primary endpoints as well as to validate surrogate and clinical endpoints. The availability of new endpoints could improve clinical care, lead to new therapeutic targets and help more efficiently evaluate the effects of interventions aimed at stopping or slowing the progression of DRD.
The Mary Tyler Moore Vision Initiative seeks to address the unmet need for new endpoints in clinical care and research of DRD. Recent advances in imaging and technology allow us to more fully characterize changes in the retina and to measure aspects of visual function beyond best corrected central visual acuity. The first step in meeting the unmet need for new endpoints in clinical care and research of DRD is to administer state-of-the art imaging and functional testing to patients with diabetes, ranging from those who are newly diagnosed to those with proliferative disease or macular edema warranting treatment. As such, we have proposed two prospective, longitudinal clinical studies that will help validate potential endpoints of interest based on initial discussions at the MTM Vision Endpoints Workshop held in Ann Arbor in the Fall of 2022, and additional protocol development meetings online and in-person over the last year.
The first study will enroll a cohort of patients across the severity spectrum of DRD and characterize their functional and structural retinal changes over 4 years in the natural history of the disease. The second study will recruit patients who are beginning intravitreal anti-VEGF therapy for center-involved diabetic macular edema and characterize baseline retinal abnormalities and longitudinal changes over a year of treatment. Study procedures are anticipated to include manifold quantitative contrast sensitivity testing, RETeval electroretinography, objective field analyzer perimetry, ultrawide field fundus photography and fluorescein angiography, optical coherence tomography and OCT angiography. The primary objective for these studies is to define the ocular structural and functional characteristics of people with diabetes, covering a broad range of diabetes duration and disease severity in eyes over the natural history of the disease and in eyes with center-involved diabetic macular edema undergoing intravitreal anti-vascular endothelial growth factor therapy. Secondary study objectives include the following:
We aim to begin these studies in 2024, possibly as a collaborative effort between MTM Vision and the DRCR Retina Network, an NIH-supported consortium of clinical sites performing research in retinal disease. Additional discussions are also underway to leverage other ongoing clinical research to provide supplemental endpoint validation datasets.