Retinal Oxygen Extraction Fraction Research Articles

Relating glaucomatous visual field loss to retinal oxygen delivery and metabolism.

To test the hypothesis that visual field (VF) loss is associated with decreased retinal blood flow, oxygen delivery and metabolism, and with increased retinal oxygen extraction fraction (OEF) in glaucomatous individuals. Glaucomatous subjects underwent automated perimetry, dual wavelength scanning laser ophthalmoscopy and Doppler optical coherence tomography imaging in order to measure mean deviation, central retinal arterial and venous diameter equivalents (CRAE and CRVE), oxygen saturation levels and total retinal blood flow (TRBF), respectively. Retinal oxygen delivery, metabolism and extraction fraction were derived from measurements of oxygen saturation and blood flow. Twenty eyes of 14 subjects were included in the study. Mean deviation was on average -13.76±8.70 dB. Mean CRAE and CRVE were 126±28 and 191±35μm, respectively. Mean TRBF and oxygen delivery were 34.3± 11.7μl/min and 6.5±2.6μl O2 /min, respectively. Mean oxygen metabolism and extraction fraction were 2.1±0.94μl O2 /min and 0.34±0.15, respectively. Visual field (VF) loss was associated with reduced CRAE and CRVE, TRBF and oxygen delivery and associated with increased OEF. Combined measurements of retinal blood flow and oxygen saturation in glaucomatous individuals suggest VF loss is associated with impaired oxygen delivery and augmented OEF.

Retinal Vascular and Oxygen Temporal Dynamic Responses to Light Flicker in Humans.

PurposeTo mathematically model the temporal dynamic responses of retinal vessel diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF) to light flicker and to describe their responses to its cessation in humans.MethodsIn 16 healthy subjects (age: 60 ± 12 years), retinal oximetry was performed before, during, and after light flicker stimulation. At each time point, five metrics were measured: retinal arterial and venous D (DA, DV) and SO2 (SO2A, SO2V), and OEF. Intra- and intersubject variability of metrics was assessed by coefficient of variation of measurements before flicker within and among subjects, respectively. Metrics during flicker were modeled by exponential functions to determine the flicker-induced steady state metric values and the time constants of changes. Metrics after the cessation of flicker were compared to those before flicker.ResultsIntra- and intersubject variability for all metrics were less than 6% and 16%, respectively. At the flicker-induced steady state, DA and DV increased by 5%, SO2V increased by 7%, and OEF decreased by 13%. The time constants of DA and DV (14, 15 seconds) were twofold smaller than those of SO2V and OEF (39, 34 seconds). Within 26 seconds after the cessation of flicker, all metrics were not significantly different from before flicker values (P ≥ 0.07).ConclusionsMathematical modeling revealed considerable differences in the time courses of changes among metrics during flicker, indicating flicker duration should be considered separately for each metric. Future application of this method may be useful to elucidate alterations in temporal dynamic responses to light flicker due to retinal diseases.

A Method for Combined Retinal Vascular and Tissue Oxygen Tension Imaging

The retina requires adequate oxygenation to maintain cellular metabolism and visual function. Inner retinal oxygen metabolism is directly related to retinal vascular oxygen tension (PO2) and inner retinal oxygen extraction fraction (OEF), whereas outer retinal oxygen consumption (QO2) relies on oxygen availability by the choroid and is contingent upon retinal tissue oxygen tension (tPO2) gradients across the retinal depth. Thus far, these oxygenation and metabolic parameters have been measured independently by different techniques in separate animals, precluding a comprehensive and correlative assessment of retinal oxygenation and metabolism dynamics. The purpose of the current study is to report an innovative optical system for dual oxyphor phosphorescence lifetime imaging to near-simultaneously measure retinal vascular PO2 and tPO2 in rats. The use of a new oxyphor with different spectral characteristics allowed differentiation of phosphorescence signals from the retinal vasculature and tissue. Concurrent measurements of retinal arterial and venous PO2, tPO2 through the retinal depth, inner retinal OEF, and outer retinal QO2 were demonstrated, permitting a correlative assessment of retinal oxygenation and metabolism. Future application of this method can be used to investigate the relations among retinal oxygen content, extraction and metabolism under pathologic conditions and thus advance knowledge of retinal hypoxia pathophysiology.

The Effects of Diabetic Retinopathy Stage and Light Flicker on Inner Retinal Oxygen Extraction Fraction

PurposeWe determined the effects of light flicker and diabetic retinopathy (DR) stage on retinal vascular diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF).MethodsSubjects were categorized as nondiabetic control (NC, n = 42), diabetic with no clinical DR (NDR; n = 32), nonproliferative DR (NPDR; n = 42), or proliferative DR (PDR; n = 14). Our customized optical imaging system simultaneously measured arterial and venous D (DA, DV) and SO2 (SO2A, SO2V) before and during light flicker. Inner retinal OEF was derived from SO2 values. Light flicker–induced ratios of metrics (DAR, DVR, SO2AR, SO2VR, OEFR) were calculated.ResultsArterial D was larger in NPDR compared to NC (P = 0.01) and PDR (P = 0.002), whereas DV was similar among groups (P ≥ 0.16). Light flicker increased DA and DV (P ≤ 0.004), but DAR and DVR were similar among groups (P ≥ 0.09). Arterial SO2 was higher in all groups compared to NC (P ≤ 0.02) and higher in PDR compared to NDR and NPDR (P<0.001). Arterial SO2 did not change with light flicker (P ≥ 0.1). Venous SO2 was higher in NPDR and PDR compared to NC and NDR (P ≤ 0.02). Light flicker increased SO2V in NC, NDR, and PDR (P ≤ 0.003), and SO2VR was lower in NPDR compared to NC and NDR (P ≤ 0.05). Inner retinal OEF was lower in NPDR compared to NDR and PDR (P ≤ 0.02). Light flicker decreased OEF (P ≤ 0.03), but OEFR was greater in NPDR compared to NC and NDR (P ≤ 0.03).ConclusionsThe findings of alterations in retinal D, SO2, OEF, and their light flicker–induced responses at stages of DR may be useful to elucidate the pathophysiology of DR.

Inner Retinal Oxygen Extraction Fraction in Response to Light Flicker Stimulation in Humans

Light flicker has been shown to stimulate retinal neural activity, increase blood flow, and alter inner retinal oxygen metabolism (MO2) and delivery (DO2). The purpose of the study was to determine the change in MO2 relative to DO2 due to light flicker stimulation in humans, as assessed by the inner retinal oxygen extraction fraction (OEF). An optical imaging system, based on a modified slit lamp biomicroscope, was developed for simultaneous measurements of retinal vascular diameter (D) and oxygen saturation (SO2). Retinal images were acquired in 20 healthy subjects before and during light flicker stimulation. Arterial and venous D (DA and DV) and SO2 (SO2A and SO2V) were quantified within a circumpapillary region. Oxygen extraction fraction was defined as the ratio of MO2 to DO2 and was calculated as (SO2A - SO2V)/SO2A. Reproducibility of measurements was assessed. Coefficients of variation and intraclass correlation coefficients of repeated measurements were <5% and ≥0.83, respectively. During light flicker stimulation, DA, DV , and SO2V significantly increased (P ≤ 0.004). Oxygen extraction fraction was 0.37 ± 0.08 before light flicker and significantly decreased to 0.31 ± 0.07 during light flicker (P = 0.001). Oxygen extraction fraction before and during light flicker stimulation is reported in human subjects for the first time. Oxygen extraction fraction decreased during light flicker stimulation, indicating the change in DO2 exceeded that of MO2. This technology is potentially useful for the detection of changes in OEF response to light flicker in physiological and pathological retinal conditions.

Response of inner retinal oxygen extraction fraction to light flicker under normoxia and hypoxia in rat.

Oxygen extraction fraction (OEF), defined by the ratio of oxygen metabolism (MO2) to delivery (DO2), determines the level of compensation of MO2 by DO2. In the current study, we tested the hypothesis that inner retinal OEF remains unchanged during light flicker under systemic normoxia and hypoxia in rats due to the matching of MO2 and DO2. Retinal vascular oxygen tension (PO2) measurements were obtained in 10 rats by phosphorescence lifetime imaging. Inner retinal OEF was derived from vascular PO2 based on Fick's principle. Measurements were obtained before and during light flicker under systemic normoxia and hypoxia. The effects of light flicker and systemic oxygenation on retinal vascular PO2 and OEF were determined by ANOVA. During light flicker, retinal venous PO2 decreased (P < 0.01, N = 10), while inner retinal OEF increased (P = 0.02). Under hypoxia, retinal arterial and venous PO2 decreased (P < 0.01), while OEF increased (P < 0.01). The interaction effect was not significant on OEF (P = 0.52), indicating the responses of OEF to light flicker were similar under normoxia and hypoxia. During light flicker, OEF increased from 0.46 ± 0.13 to 0.50 ± 0.11 under normoxia, while under hypoxia, OEF increased from 0.67 ± 0.16 to 0.74 ± 0.14. Inner retinal OEF increased during light flicker, indicating the relative change in DO2 is less than that in MO2 in rats under systemic normoxia and hypoxia. Inner retinal OEF is a potentially useful parameter for assessment of the relative changes of MO2 and DO2 under physiologic and pathologic conditions.

Inner Retinal Oxygen Extraction Fraction in Rat

Oxygen extraction fraction (OEF), defined by the ratio of oxygen consumption to delivery, may be a useful parameter for assessing the retinal tissue status under impaired circulation. We report a method for measurement of inner retinal OEF in rats under normoxia and hypoxia based on vascular oxygen tension (PO(2)) imaging. Retinal vascular PO(2) measurements were obtained in 10 rats, using our previously developed optical section phosphorescence lifetime imaging system. Inner retinal OEF was derived from retinal vascular PO(2) measurements based on Fick's principle. Measurements of inner retinal OEF obtained under normoxia were compared between nasal and temporal retinal sectors and repeatability was determined. Inner retinal OEF measurements obtained under normoxia and hypoxia were compared. Retinal vascular PO(2) and inner retinal OEF measurements were repeatable (ICC ≥ 0.83). Inner retinal OEF measurements at nasal and temporal retinal sectors were correlated (R = 0.71; P = 0.02; n = 10). Under hypoxia, both retinal arterial and venous PO(2) decreased significantly as compared with normoxia (P < 0.001; n = 10). Inner retinal OEF was 0.46 ± 0.13 under normoxia and increased significantly to 0.67 ± 0.16 under hypoxia (mean ± SD; P < 0.001; n = 10). Inner retinal OEF is a promising quantitative biomarker for the adequacy of oxygen supply for metabolism under physiologically and pathologically altered conditions.