Diabetic Retinal Neurodegeneration in Youth Onset Diabetes

Project Summary Diabetic retinopathy (DR) is a common complication of diabetes that is traditionally associated with observable structural alterations in the retinal blood vessels, including microaneurysms, hemorrhages and exudates. Emerging research has shown that retinal neurodegeneration (DRN), or damage to the retinal neural tissue, precedes the manifestation of vascular abnormalities, and may be an early component of diabetic retinal disease. The use of optical coherence tomography (OCT) imaging allows precise and reproducible measurements of the retinal layers that can distinguish small alterations in thickness, that are associated with DRN in both type 1 (T1D) and type 2 diabetes (T2D). Several cross-sectional studies in adults with diabetes have shown reduced thickness of the retinal nerve fiber layer (RNFL) and ganglion cell- inner plexiform layer (GC-IPL) layers, as compared to healthy controls, but there is limited data available in the pediatric population. With prior NEI funding (R01EY033233) we conducted a rigorous, prospective trial from 2022-2024 resulting in a well-characterized cohort of 380 youth with type 1 and type 2 diabetes, 25 youth with prediabetes, and 21 age-matched healthy controls who underwent fundus photography for diabetic retinopathy screening using autonomous AI and point of care OCT imaging (NCT05463289). Utilizing this well described cohort with robust clinical data and quality fundus and OCT images, we hypothesize that thinning of the neural retina layers (RNFL and GC-IPL) will be more pronounced in youth with longer durations of diabetes, as well as worse glycemic control. Further, we hypothesize that DRN will be present in youth with prediabetes compared to healthy controls, but will be more severe in those with youth onset type 2 diabetes. In this proposal, we aim to describe retinal neurodegeneration in youth onset diabetes. In a diverse cohort of youth with T1D, Aim 1 will determine if neuroretinal thickness is associated with duration of diabetes (Aim 1a), assess for associations of neuroretinal thickness with race and ethnicity and social determinants of health (Aim 1b), and assess the association of neuroretinal thickness with use of diabetes technologies and glycemic control (Aim 1c). In Aim 2, we will compare neuroretinal thickness between youth with T2D, prediabetes and youth without diabetes (Aim 2a), assess for associations of neuroretinal thickness with race and ethnicity and social determinants of health (Aim 2b), and assess the association of neuroretinal thickness with GLP1 use (Aim 2c). Earlier identification of diabetic retinal disease will further our understanding of alterations in the neuroretina and may optimize potential interventions to improve visual outcomes for the growing population of youth with diabetes.