Relationship Between Retinal Fractal Dimension and Nonperfusion in Diabetic Retinopathy on Ultrawide-Field Fluorescein Angiography

Purpose: To correlate fractal dimension (FD) of the retinal vasculature with the extent of retinal nonperfusion area in diabetic retinopathy (DR) on ultrawide-field fluorescein angiography (FA). Design: Cross-sectional study. Methods: Baseline Optos 200Tx ultrawide-field FA images of 80 eyes with DR from the DAVE (NCT01552408) and RECOVERY (NCT02863354) studies were stereographically projected at the Doheny Image Reading Center. The retinal vasculature was extracted from an early-phase FA frame by exploiting the elongated nature of the vessels and then skeletonized for calculation of FD using a box-counting method. The nonperfusion area was delineated by 2 independent, reading center–certified graders who were masked to the study groups and who were using a standardized protocol and then computed in millimeters squared. Results: While no difference in FD was observed for the entire retina in DR compared with normal control subjects, a significantly smaller FD was found in the far-periphery of the DR eyes (P < .001). FD for the entire retina was negatively associated with global nonperfusion area (R = −0.44; P < .001), and this relationship was also present within the 3 concentric retinal zones (posterior: R = −0.31, P = .016; midperiphery: R = −0.35, P = .007; and far periphery: R = −0.31, P = .015). Conclusions: Peripheral FD on ultrawide-field FA is reduced in DR eyes compared with normal eyes and is correlated with severity of retinal nonperfusion. FD can be calculated automatically without the need for correction of peripheral distortion, and therefore it may prove to be a useful surrogate biomarker when precise quantification of nonperfusion is not feasible.