Characterization of vascular responses to intravitreal anti-VEGF injections in diabetic retinopathy

Diabetic retinopathy (DR) is the most prevalent retinal vascular disease worldwide causing visual impairment and blindness in nearly 8 million Americans. Over the past two decades, the use of intravitreal anti-VEGF therapy for proliferative DR has been studied extensively and has been shown to be effective for improving visual acuity and preventing progression. However, studies regarding the impact of VEGF blockage on the status of retinal vascular perfusion have produced controversial and contradictory findings. Central to this dilemma is tremendous variability and weak correlation of treatment-monitoring biomarkers to clinical outcomes. Vascular metrics such as capillary density and foveal avascular zone area as currently measured have not proven consistently sensitive enough to detect and monitor clinical DR improvement or progression. To address this knowledge gap, we propose the use of two non-invasive high-resolution retinal imaging techniques to identify subclinical microvascular changes, quantify perfusion, and visualize cellular changes in DR, namely adaptive optics scanning light ophthalmoscopy (AOSLO) and optical coherence tomography angiography (OCTA). In our preliminary work, we developed several highly-reliable retinal vascular metrics, developed age/race/sex- matched normative databases, and showed that categorized perfusion changes, outperformed currently available vascular metric for monitoring anti-VEGF treatment response in DR. Our hypothesis is that our new approaches to AOSLO and OCTA quantitative image analysis will generate biomarkers which are more sensitive and better suited to guide treatment by overcoming clinical uncertainties in DR management. We propose to conduct a prospective cohort study using retinal imaging and clinical data collection to 1) further improve our AO ophthalmoscope for precise structural and functional measurements, 2) validate our custom vascular metrics for early DR detection and as objective indicators of disease severity, and 3) characterize short-term anti-VEGF treatment response in DR. To accomplish these important goals, the proposed project brings together expertise in optical design and engineering, retinal imaging, and ophthalmology.