Combined Multimodal Analysis of Peripheral Retinal and Macular Circulation in Diabetic Retinopathy (COPRA Study)

To systematically examine the relationships between the microvascular indices that are measured on OCT angiography (OCTA) and the presence and extent of peripheral nonperfusion in persons with diabetic retinopathy.

A retrospective cross-sectional study of patients who had varying degrees of diabetic retinopathy. The study sample was recruited from 2 large tertiary referral retina clinics.

In total, 82 eyes of 45 patients with varying degrees of diabetic retinopathy were enrolled and analyzed.

Relationships between peripheral ischemia measured on fluorescein angiography (FA) and OCTA metrics, including foveal avascular zone (FAZ) and vessel density measurements.

A significant decrease in mean signal index in both the superficial and deep plexus and binarized flow index in the superficial plexus were found with increasing duration of diabetes mellitus. OCT and OCTA grading showed increasing central macular thickness and prevalence of microvascular abnormalities in the superficial and deep capillary bed with worse retinopathy as measured on the Diabetic Retinopathy Severity Scale. FAZ area and major axis and minor axis length were strongly associated with diabetic retinopathy severity. On classifying eyes into tertiles of peripheral ischemia measured on FA, significant increases in various FAZ metrics, including FAZ area and minor axis length, were noted. Statistically worsening of FAZ OCTA metrics was only seen between tertiles 2 and 3, indicating a non-linear relationship. The presence of neovascularization of the disc, neovascularization elsewhere, or intraretinal microvascular abnormality was associated with a significant increase in FAZ major axis length in the superficial plexus and a significant decrease in binarized flow index in the deep plexus.

OCTA metrics are indicators of the severity of peripheral retinal nonperfusion. However, the central ischemic index did not exhibit a linear relationship with peripheral capillary nonperfusion. Our findings suggest that a rise in intraocular vascular endothelial growth factor as a consequence of mild peripheral capillary nonperfusion may play a compensatory role in maintaining the central macular microcirculation. Further investigations with studies employing longitudinal design will improve our understanding of the relationship between macular microcirculation and peripheral ischemia.