Jennifer Sun, MD, MPH, Science Co-Director of the Mary Tyler Moore Vision Initiative and Professor of Ophthalmology at Harvard Medical School, summarized efforts for an updated DRD staging system that would include retinal vascular function, neural function deterioration, biochemical markers, systemic health, and other parameters, including quality of life and visual function.
10 The MTM Vision working group reviews have revealed significant gaps in current knowledge of endpoints in clinical care and research of DRD, particularly for guiding early-stage interventions.
2–7 The first step in meeting the unmet need for new endpoints in DRD is to comprehensively validate potential endpoints of interest using state-of-the art imaging and functional testing in patients with diabetes, ranging from those who are newly diagnosed to those with proliferative disease or macular edema warranting treatment. As such, MTM Vision has developed 2 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,
1 and subsequent protocol development meetings and MTM Vision working group papers.
2,4–7 The identification of priority variables (
Table 1) provides a foundation for future studies aiming to validate these factors as reliable clinical endpoints. Over the last year, MTM Vision has refined these studies in collaboration with the DRCR Retina Network (DRCR), a National Institutes of Health-funded collaborative consortium of sites across North America, which performs clinical studies in retinal disease. Alongside MTM Vision, Breakthrough T1D (formerly JDRF) has committed support for these studies and for the data standardization efforts that will allow mapping of study variables to common data elements models.
8 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-vascular endothelial growth factor (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 quantitative contrast sensitivity testing, RETeval electroretinography, objective field analyzer perimetry, ultrawide field fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Thus, the studies will define the relationships between standard structural parameters with changes in rod and cone photoreceptor pathways. The primary objective for these studies, which are both expected to start enrolling patients in 2025, 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 undergoing treatment for diabetic macular edema. Additional discussions are underway to leverage other ongoing clinical research to provide supplemental endpoint validation datasets and to build an international network of centers able to draw on data from large cohorts to efficiently evaluate the prognostic and predictive benefit of risk factors, imaging technologies, functional assessments, and other novel endpoints in service of accelerating development and regulatory approval of potential new therapies for DRD. Building a strong partnership among academic, industry, and regulatory institutions is needed to encourage the incorporation of promising structural and functional variables, standardize variables across datasets in accordance with common data element models, promote sharing of clinical and research datasets, and support the development and validation of new primary endpoints for DRD.