Morphology of vascular network in eyes with diabetic macular edema varies based on tolerance of aflibercept treatment interval length: Preliminary findings

Diabetic macular edema is a leading cause of vision loss in diabetic patients. The underlying cause for the onset of DME is 1) the long term presence of hyperglycemia and the eventual degradation of the blood-retinal barrier (BRB) via an uptick in vascular endothelial growth factor (VEGF); VEGF increases the permeability of the blood retinal barrier and alters the length of capillaries, thereby inhibiting the ability of these vessels in performing their primary function of filtration. The lack of a proper filtration system in combination with the ongoing change in intra-retinal vasculature that stems from it, results in the eventual loss of visual acuity in DME patients. Due to the large role in which VEGF plays in acting as a catalyst for the onset of DME, current treatments now focus on utilizing anti-VEGF therapy as a first line treatment for DME. Anti-VEGF therapy improves clinical outcomes in the form of improved visual acuity and reduction in macular edema. Anti-VEGF treatments also have a peripheral effect of modifying the disease burden and allowing for extended time in between treatments. However, there is still a void in understanding how anti-VEGF affects the underlying pathophysiology. This study focuses on using quantification of the geometric properties of vasculature on Fluorescein Angiography(FA) to understand the impact anti-VEGF treatment has on retinal vascular dynamics. We hypothesize that vasculature disorder, due to VEGF action, differs across patients and can be modeled mathematically to identify candidates for anti-VEGF treatment. We use VaNgOGH, a Hough transform-based descriptor to model the disorder of the retinal vascular network on baseline FA of patients subsequently treated with intravitreal anti-VEGF therapy (aibercept). VaNgOGH computes local measures of vessel-curvature and identifies dominant peaks in the accumulator space. We explored the differences in such features on baseline FA between eyes tolerating extended dosing interval (N=15) and those eyes requiring more frequent dosing (N=12), based on initial response following treatment interval extension. The cross-validated AUC was found to be 0.73±0.1 using VaNgOGH. The variance of local orientations showed a statistically significant difference (p=0.008) between the two categories, unlike clinical parameters on baseline OCT. Our results suggest there may be fundamental differences in localized vessel orientations between eyes that will exhibit favorable response to extended interval aibercept dosing and eyes that require more frequent dosing.