Peripapillary Neurovascular Coupling is Compromised in Early Diabetic Retinopathy

Abstract

Purpose : Retinal nerve fiber layer (RNFL) thickness is known to be decreased in diabetic patients with minimal or even no diabetic retinopathy (DR). However, the putative contribution of radial peripapillary capillaries (RPC) to these neuroretinal changes has not been addressed. We designed a cross-sectional, prospective, observational study to evaluate how RNFL thickness correlates with RPC density in the early stages of DR, using optical coherence tomography angiography (OCT-A).

Methods : Consecutive type 1 and 2 adult diabetic patients with or without DR (up to ETDRS Level 53) were invited to participate. Patients with proliferative DR or diabetic macular edema were excluded. OCT-A (Avanti RTVue-XR 100, Optovue Inc) was used for RNFL thickness and RPC density analysis. A custom-developed macro (Fiji, SciJava Consortium) was employed to exclude the contribution of the large blood vessels in RPC density. Seven-field photographs of the fundus were taken for DR staging. Diabetic eyes were divided in 2 groups: without DR (NoDR) and nonproliferative DR (NPDR). A population of healthy subjects was used as control. Mixed-effects univariate and multivariate linear regression models were used for statistical analysis.

Results : We included 136 eyes (n=43 control; n=25 NoDR; n=68 NPDR) from 74 subjects (mean[SD] age 63.35[9.66] years). A significant decrease in RNFL thickness was found both in the NoDR (β=–8.01, P=0.003) and in the NPDR groups (β=–6.29, P=0.008), when compared to controls. A significant decrease in RPC density was also observed, even after adjusting for confounders (NoDR: β=–1.97, P=0.049; NPDR: β=–2.55, P=0.048). On univariate analysis, RNFL thickness was strongly associated with RPC density in NoDR (β=1.46, P=0.002) and in NPDR eyes (β=0.58, P=0.013), but not in the control group (β=–0.31, P=0.352). The significance level held for the NPDR group (β=0.57, P=0.016) and it was marginally significant for the NoDR group (β=0.99, P=0.054) after adjusting for age and spherical equivalent. Time since the diagnosis of diabetes was found to negatively correlate with RPC density (β=–0.07, P=0.037).

Conclusions : This study provides novel mechanistic insight into DR, demonstrating that peripapillary neurovascular coupling is compromised early in the course of DR. Whether the reduction in RPC density predates RNFL thinning or is a consequence of neuronal loss and reduced demands for blood supply warrants further research.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.