This proposal aims to study retinal blood flow, detected by non-invasive imaging, during medical treatments for diabetic retinopathy. Success of this proposal will lead to the development of non-invasive measurements that can guide clinicians as they manage patients with sight threatening complications of diabetic retinopathy.
Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Current therapies that achieve long-lasting durable outcome include laser panretinal photocoagulation and laser macular therapy, while pharmacotherapy requires high intensity treatment with treatment interruption could lead to disastrous outcomes. Therefore, there is a heightened need to study ocular parameters are associated with favorable therapeutic outcomes. Using high-resolution quantitative imaging of retinal hemodynamics, we propose to develop quantitative tools to measure macular perfusion, Currently, approving new therapies relies on structural measures of retinal thickness (OCT), or retinal hemorrhages/aneurysms (color photography and ETDRS scale). While these are important test, they do not directly capture the functional effects on retinal vascular function and hemodynamics. In effect, we do not have the necessary tools to study whether any of these therapies are associated with improved vascular flow and hemodynamics. To address this gap in our knowledge, we have harnessed the power of the precision and high resolution of adaptive optics scanning laser ophthalmology (AOSLO) as well the speed and non-invasiveness of OCT angiography. We hypothesize that macular hemodynamics quantified with our approach will accurately reflect the baseline vascular function in eyes with DR. We further hypothesize that therapies that achieve durable positive outcomes will be associated with improvements in retinal hemodynamics, leading to long-term truly fundamental improvement in DR outcome. To examine this hypothesis, we will study the effect of current standard of care therapies on macular hemodynamics. In Aim 1, We will implement technical advances to enhance the clinical performance of the technology and improve its throughput for clinical use. In Aim 2, we will study the effect of standard-of-care antiVEGF therapy on macular hemodynamics in eyes with diabetic macular edema. Eyes will have hemodynamic studies at baseline and then every 6 months for two year to examine these changes over time. Finally, in Aim 3, we will compare the effect of antiVEGF and panretinal photocoagulation on macular hemodynamics in eyes with proliferative diabetic retinopathy. These studies will provide important insights into the mechanistic effects of these therapies and uncover critical hemodynamic changes that characterize eyes that have durable positive responses. The tools developed in this proposal can then be used to quantify the efficacy of novel therapies introduced in the clinical arena by evaluating them using more physiologic outcomes.