Imaging of Retinal Oxygen Delivery and Metabolism in Diabetic Retinopathy

Abstract

Purpose : Diabetic retinopathy (DR) is a major complication of diabetes and the leading cause of vision loss in working age adults. With progression of DR, retinal vascular abnormalities and tissue hypoxia are thought to contribute to the development of vision-threatening pathologies. Since there are no available methods to measure retinal tissue oxygenation in human subjects, assessment of the rate of oxygen metabolism (MO₂) can provide essential information about the ability of cells to generate energy and perform visual processing. The purpose of the current study was to test the hypothesis that MO₂ is impaired at progressive stages of DR, concurrent with a reduction in the rate of oxygen delivery (DO₂) and elevation in the fraction of oxygen extraction (OEF).

Methods : The study was performed in 51 subjects, categorized in 4 groups: non-diabetic (N=14), no DR (N=9), non-proliferative DR (NPDR) (N=18), and treated proliferative DR (PDR) (N=10). Dual wavelength oximetry and Doppler OCT imaging were performed to measure retinal vascular oxygen saturation and total retinal blood flow, respectively. DO₂ and MO₂ were derived based on measurements of oxygen saturation and blood flow. OEF was calculated as the ratio of MO₂ to DO₂. General linear models were generated to compare oxygen metrics between non-diabetic and each DR group.

Results : Mean age was not statistically different among the 4 groups (P=0.14). In the non-diabetic group, DO₂, MO₂, and OEF were 8.90±2.90 uLO₂/min, 3.50±1.05 uLO₂/min, and 0.40±0.08, respectively. DO₂ was lower in NPDR (β=-1.91 uLO₂/min; P=0.05) and PDR (β=-3.62 uLO₂/min; P=0.002) compared to the non-diabetic group. Likewise, MO₂ was lower in NPDR (β=-0.85 uLO₂/min; P=0.05) and PDR (β=-1.45 uLO₂/min; P=0.005). OEF was not significantly different between non-diabetic and DR groups (P>0.45). With optimal binning of MO₂ with respect to DR stage, all non-diabetic and no DR subjects had MO₂>1.96 uLO₂/min. In contrast, 11/18 (61%) and 4/10 (40%) of NPDR and PDR subjects had MO₂<1.96 uLO₂/min. MO₂ was linearly related to DO₂ (R=0.85; P<0.001) and OEF (R=0.47; P<0.001), while OEF and DO₂ were not correlated (R=-0.01; P=0.94).

Conclusions : The results demonstrated reductions of DO₂ and MO₂ concurrent with unchanged OEF in NPDR and PDR. Further studies are needed to investigate the coupling of these oxygen metrics to help advance the understanding of DR pathophysiology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.