February 2013
Volume 54, Issue 2
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Clinical Trials  |   February 2013
Measurement of Retinal Oxygen Saturation in Patients with Chronic Obstructive Pulmonary Disease
Author Affiliations & Notes
  • Stefan Palkovits
    From the Department of Clinical Pharmacology, the
  • Michael Lasta
    From the Department of Clinical Pharmacology, the
  • Agnes Boltz
    From the Department of Clinical Pharmacology, the
    Center for Medical Physics and Biomedical Engineering, and the
  • Doreen Schmidl
    From the Department of Clinical Pharmacology, the
  • Semira Kaya
    From the Department of Clinical Pharmacology, the
  • Martin Hammer
    Department of Experimental Ophthalmology, Jena University Hospital, Jena, Germany; and the
  • Beatrice Marzluf
    From the Department of Clinical Pharmacology, the
  • Alina Popa-Cherecheanu
    Department of Ophthalmology, Emergency University Hospital, Bucharest, Romania.
  • Sophie Frantal
    Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria; the
  • Leopold Schmetterer
    From the Department of Clinical Pharmacology, the
    Center for Medical Physics and Biomedical Engineering, and the
  • Gerhard Garhöfer
    From the Department of Clinical Pharmacology, the
  • Corresponding author: Gerhard Garhöfer, Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18‐20, A-1090 Vienna, Austria; gerhard.garhoefer@meduniwien.ac.at  
Investigative Ophthalmology & Visual Science February 2013, Vol.54, 1008-1013. doi:10.1167/iovs.12-10504
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      Stefan Palkovits, Michael Lasta, Agnes Boltz, Doreen Schmidl, Semira Kaya, Martin Hammer, Beatrice Marzluf, Alina Popa-Cherecheanu, Sophie Frantal, Leopold Schmetterer, Gerhard Garhöfer; Measurement of Retinal Oxygen Saturation in Patients with Chronic Obstructive Pulmonary Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(2):1008-1013. doi: 10.1167/iovs.12-10504.

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      © 2016 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose.: There is growing evidence that disturbances in retinal oxygenation may trigger ocular diseases. New instruments allow for the noninvasive measurement of retinal oxygen saturation in humans. The present study was designed to investigate the retinal oxygen saturation in patients with chronic obstructive pulmonary disease (COPD). This was also done in an effort to test the validity of retinal oxygenation measurements with a retinal vessel analyzer.

Methods.: In all, 16 patients with severe COPD grade 4 who were on long-term oxygen treatment were included in the study. For each patient two identical study days were scheduled. Measurements of retinal arterial and venous oxygen saturation were done using a commercially available instrument for retinal oxygen analysis. Peripheral arterial oxygen saturation values were analyzed with pulse oximetry and via a capillary blood sample drawn from the earlobe. Measurements were performed during oxygen treatment and during a period without oxygen supplementation. Analysis of all images for retinal oxygen saturation quantification was done by a masked investigator. Analysis was done using Pearson's correlation and a multivariate regression model.

Results.: Arterial and venous retinal oxygen saturation decreased significantly after the cessation of the oxygen therapy. The arteriovenous oxygen difference was unchanged while breathing ambient air or pure oxygen–enriched air. With both Pearson's correlation and the multivariate model, we found significant positive correlation coefficients between retinal arterial and peripheral arterial oxygen saturation as assessed with pulse oximetry as well as between retinal arterial and peripheral arterial oxygen saturation measured in blood samples. The change of oxygen saturation after discontinuation of oxygen supplementation showed a good correlation between retinal arterial oxygen saturation and peripheral arterial oxygen saturation (r = 0.53, P < 0.05). Reproducibility on the two study days was high.

Discussion.: The present study shows a good correlation between retinal arterial and peripheral arterial oxygen saturation indicating good validity of the technique. (ClinicalTrials.gov number, NCT00999024.)

Introduction
A constant supply with oxygen is crucial to maintain adequate organ function, in particular for tissues with high energy demand such as the retina. Thus, it does not come as a surprise that even small alterations of retinal oxygen tension may lead to tissue hypoxia and neuronal death. Along this line of thought, evidence has been provided that ocular diseases such as glaucoma 14 or diabetic retinopathy 59 are paralleled with impaired tissue oxygenation and/or hypoxia. 
In recent years, several attempts have been made to develop a method for measuring oxygen tension in vivo. These methods include oxygen-sensitive microelectrodes, 10 oxygen-quenching phosphorescence technique, 11 or functional magnetic resonance tomography. 12 Most of these methods are invasive and, thus, limited to animal studies. In recent years, systems for the noninvasive determination of oxygen in major branches of the retinal vessels were developed. 13,14 Validation of these new techniques is difficult, however, because no gold-standard technique for the measurement of retinal oxygen saturation is currently available. 
The current study was designed to investigate the retinal arterial and venous oxygen saturation in patients with severe chronic obstructive pulmonary disease (COPD). These patients show, because of their underlying disease, decreased oxygen saturation in arteries and thus allow for the investigation whether systemic hypoxia is reflected in the oxygen measurement of the retina. 
Methods
Subjects
In the present study, 16 patients with severe COPD stage 4 were included. All study procedures were explained to the participating patients and an informed consent was obtained prior to inclusion. The study was performed in accordance with the tenets of the Declaration of Helsinki and Good Clinical Practice (ClinicalTrials.gov number, NCT00999024). The study was approved by the ethics committee of the Medical University of Vienna, Austria. Severe COPD was defined as a forced expiratory volume of less than 30% (FeV1% < 30) and a need of long-term oxygen treatment. 15 As such, all patients used portable oxygen concentrator devices for additional oxygen supplementation. 
Prior to inclusion, a screening examination was performed. The screening examination included measurement of blood pressure and heart rate (HR), recording of medical history and concomitant medication, best corrected visual acuity, and slit-lamp biomicroscopy as well as indirect fundoscopy. Patients with ocular pathologies were excluded from the study. The eye with the better visual acuity was chosen as the study eye. 
Experimental Paradigm
Two identical study days were scheduled for all patients. On the study days the patients arrived at our department with their ongoing oxygen treatment. The baseline measurements, including retinal oxygen saturation and peripheral arterial oxygen saturation values as measured with two different methods, were obtained while the patients were on oxygen supplementation. The patients were then asked to stop the oxygen supply for 20 minutes. At the end of the 20-minute period, arterial and venous retinal oxygen saturation as well as peripheral arterial oxygen saturation were determined again. 
Measurement of Retinal Oxygen Saturation
Arterial and venous retinal oxygen saturation levels were obtained using the retinal vessel analyzer (RVA) 16 coupled to an oxygen module (Imedos, Jena, Germany). This technique was described previously in detail. 9,14 Briefly, the evaluation of retinal oxygen saturation in the vessels of the posterior pole of the human eye is based on the spectral analysis of light with selected wavelengths, which is reflected at the fundus. Two fundus pictures with wavelengths of 610 and 545 nm, respectively, were taken with a fundus camera. Oxygenated hemoglobin has a different light absorption characteristic compared with that of nonoxygenated hemoglobin: 548 nm is the isosbestic wavelength defined as the point in the light spectrum where oxygenated and nonoxygenated hemoglobin show identical absorption. Oxygenated hemoglobin is nearly transparent if it is illuminated with light with 610 nm. This relation and the difference in contrast at these wavelengths enable determination of the relation between oxygenated and total hemoglobin, the so-called oxygen saturation. The arteriovenous (AV) oxygen difference was calculated as the difference between arterial and venous oxygen saturation levels. 
The measuring procedure and the subsequent image analysis were performed as published previously. 8 Briefly, fundus images with the optic nerve head in center were taken. Oxygen saturation was measured in all vessels in a peripapillary annulus, with an inner radius of 1 and an outer radius of 1.5 disc diameters and averaged over all arterioles and venules. Vessels smaller than 70 μm and vessel crossings were excluded from the analysis. The image analysis was performed in a masked fashion by a person not involved in the study procedures (MH). 
Measurement of Systemic Hemodynamics
Blood pressure and HR were recorded for safety reasons every 5 minutes during the whole study period (HP-CMS patient monitor; Hewlett Packard, Palo Alto, CA). 
Measurement of Peripheral Arterial Oxygen Saturation via Pulse Oximeter
Peripheral arterial oxygen saturation was recorded from a finger pulse–oximetric device (HP-CMS patient monitor; Hewlett Packard). 
Measurement of the Peripheral Arterial Oxygen Saturation via Capillary Blood Analysis
In a subgroup of subjects, peripheral arterial oxygen saturation was assessed with an additional method. For this purpose, capillary blood was collected via blood drawn from the arterialized earlobe. Nicotinate plus nonylvanillamid ointment (Finalgon; Boehringer, Ingelheim, Germany) was used to induce vasodilatation. A small lancet incision was made and the blood was captured with a glass capillary. This method has previously been shown to provide a good measure of arterial oxygen saturation. 17 Blood gas analyses were done by an automatic blood gas analysis system (ABL 800 Flex; Drott Medizintechnik GmbH, Wiener Neudorf, Austria). 
Statistical Analysis
The statistical evaluation was done using a commercial statistical analysis software package (Statistica version 6.0; StatSoft, Inc., Tulsa, OK). Descriptive statistics were done for safety parameters (blood pressure and HR) and age, which are shown as mean ± SD. Oximetry data were analyzed using a repeated-measures ANOVA model. Differences between study days were calculated within the ANOVA model. To show possible relations of oximetry data among each other of Pearson's correlation coefficients and regression lines were calculated. Given that measurements in the same subjects on two different days may not be considered totally independent from each other, a multivariate regression analysis using a mixed-model approach has been used to account for the random-effects “measurement day” and “time.” To allow the reader to obtain a better interpretation of the results, Pearson's correlation and the mixed-model approach are presented separately in the Results section. For all calculations, a P < 0.05 was considered as statistically different. In addition, a Bland–Altman plot was drawn to illustrate the comparison of the methods measuring the arterial retinal and the peripheral arterial oxygen saturation. For the Bland–Altman plot, data of both study days were used. The “R-Project for Statistical Computing” (provided in the public domain by the R Foundation for Statistical Computing; http://CRAN.R-project.org) was used for the calculation of the mixed model. 
Results
In all, 13 male and three female patients with a mean age of 65.9 years (age range: 56–74 years) and a diagnosis of severe COPD were included in the study. Main patients' characteristics including systemic hemodynamic variables are given in the Table. Data of one patient had to be excluded from the analysis because of insufficient image quality of the fundus images. In addition, for three of the remaining 15 COPD patients only data for the first study day are available, because the participating subjects did not return for the second study day. 
Table. 
 
Baseline Characteristic of the Study Population at the Screening Examination
Table. 
 
Baseline Characteristic of the Study Population at the Screening Examination
Mean ± SD
Age, y 66.6 ± 5.5
SBP, mm Hg 132.5 ± 13.6
DBP, mm Hg 64.1 ± 6.7
MAP, mm Hg 85.9 ± 6.4
HR, bpm 85.9 ± 12.9
SpO2, % 93.8 ± 2.4
Baseline retinal arterial oxygenation with ongoing oxygen therapy was 92.2 ± 4.3% on the first study day and 91.8 ± 3.2% on the second study day (P = 0.35 between study days). Baseline retinal venous oxygen saturation was 67.6 ± 7.8% and 66.6 ± 5.8%, on the two study days, respectively (P = 0.33 between study days). As shown in Figure 1, cessation of oxygen delivery led to a decrease in oxygen saturation of both retinal arteries and retinal veins. Withdrawal of oxygen resulted in a decrease of retinal oxygen saturation of 2.1 ± 3.1% (P = 0.02 versus baseline) and 2.7 ± 2.8% in retinal arteries (P = 0.0039 versus baseline) and a tendency to decrease by 2.5 ± 4.7% (P = 0.06 versus baseline) and 3.1 ± 5.0% (P = 0.05 versus baseline) in retinal veins on the two study days, respectively. No difference was observed between the two study days in terms of oxygen saturation decrease either in retinal arteries (P = 0.53 difference between groups) or in retinal veins (P = 0.65 difference between groups). 
Figure 1. 
 
Retinal oxygen saturation with oxygen supplementation and after cessation of oxygen supplementation on study day 1 (A) and study day 2 (B). Data of both arteries and veins are presented. Box plots indicate mean (open square), median (line), and the 75th and 25th percentiles.
Figure 1. 
 
Retinal oxygen saturation with oxygen supplementation and after cessation of oxygen supplementation on study day 1 (A) and study day 2 (B). Data of both arteries and veins are presented. Box plots indicate mean (open square), median (line), and the 75th and 25th percentiles.
The retinal AV oxygen difference at baseline conditions was 25 ± 5% on the first study day and 25 ± 5% on the second study day (P = 0.8 between study days). After cessation of oxygen administration, the AV oxygen difference was still unchanged (25 ± 6% and 25 ± 5%, P = 0.9 between the two study days). 
Peripheral blood oxygen saturation, as assessed with the pulse oximeter, decreased from 94 ± 4% to 87 ± 3% (P < 0.01) on the first and from 94 ± 3% to 86 ± 8% (P < 0.01) on the second study day. Arterial blood oxygen saturation measured from capillary blood, which was available from seven patients only, decreased from 96 ± 1% to 91 ± 3% (P = 0.049) and from 95 ± 1% to 90 ± 5% (P = 0.037) on the two study days, respectively. Oxygen partial pressure as determined from the blood samples dropped from 83 ± 15 mm Hg during oxygen supplementation to 60 ± 13 mm Hg after cessation of oxygen breathing on the first study day and from 76 ± 20 mm Hg to 59 ± 13 mm Hg on the second study day. 
As shown in Figures 2 and 3, the correlation analyses revealed an association between both the retinal arterial and peripheral arterial oxygen saturation as assessed with the pulse oximeter (r = 0.6, P < 0.05) and the arterial oxygen saturation as measured with capillary blood gas analysis (r = 0.54, P < 0.05). Analysis of the mixed model using measurement day and measurement time as random factors showed a significant association between retinal arterial oxygen saturation as assessed with the pulse oximeter and retinal arterial oxygenation (P < 0.01), whereas no influences of the measurement day (P = 0.56) and time (P = 0.97) were observed. Similarly, using the mixed-model approach, a significant correlation between arterial oxygen saturation as measured with capillary blood gas analysis and retinal arterial oxygen saturation was found (P < 0.01). Again, the analysis revealed no influence of the random factors day (P = 0.33) and time (P = 0.84). In addition, a good correlation was observed between the change in retinal arterial oxygen saturation values after cessation of the oxygen therapy and the change in peripheral arterial oxygen saturation measured with pulse oximetry (Fig. 4, r = 0.53, P < 0.05). 
Figure 2. 
 
Correlation between peripheral arterial oxygen saturation as measured with pulse oximetry and oxygen saturation in retinal arteries (r = 0.6, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 2. 
 
Correlation between peripheral arterial oxygen saturation as measured with pulse oximetry and oxygen saturation in retinal arteries (r = 0.6, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 3. 
 
Correlation between peripheral arterial oxygen saturation as measured in capillary blood samples and retinal arterial oxygen saturation (r = 0.54, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 3. 
 
Correlation between peripheral arterial oxygen saturation as measured in capillary blood samples and retinal arterial oxygen saturation (r = 0.54, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 4. 
 
Correlation between change in peripheral arterial oxygen saturation as measured with pulse oximetry and change in retinal arterial oxygen saturation (r = 0.53, P < 0.05). Dashed lines indicate 95% confidence intervals.
Figure 4. 
 
Correlation between change in peripheral arterial oxygen saturation as measured with pulse oximetry and change in retinal arterial oxygen saturation (r = 0.53, P < 0.05). Dashed lines indicate 95% confidence intervals.
A Bland–Altman plot of retinal and peripheral oxygen saturation measurements is shown in Figure 5. In addition, there was a high correlation between the peripheral arterial oxygen saturation assessed with pulse oximetry and capillary blood analysis (r = 0.93, P < 0.05). 
Figure 5. 
 
Bland–Altman plot comparing data as obtained between peripheral arterial oxygen saturation and retinal arterial oxygen saturation.
Figure 5. 
 
Bland–Altman plot comparing data as obtained between peripheral arterial oxygen saturation and retinal arterial oxygen saturation.
Discussion
Until now two different systems for the noninvasive assessment of retinal oxygen saturation are available: The retinal oximeter (Oxymap; Oxymap ehf., Reykjavik, Iceland) and the Imedos system (RVA; Imedos), which was used in the current study. Both instruments allow for the direct and noninvasive measurement of oxygen saturation within retinal vessels. Although, for both systems, published data indicate high short- and long-term reproducibility 13,14,18 of the readings, studies about the validity of the measurements are sparse. Our data show that the peripheral arterial oxygen saturation as found in patients with severe COPD is well correlated to the readings of retinal arterial oxygen saturation. In addition, the changes in systemic arterial oxygen saturations are well reflected in the changes of retinal arterial oxygen saturation, indicating good validity of the instrument used. 
Several studies indicate a good reproducibility of oxygen saturation measurement based on the reflectrometric technique. With the same instrument as used in the current study, Hammer et al. 14 demonstrated variability with a mean SD for single-vessel measurements in five consecutively taken images in an order of 2.5% for retinal arterioles and 3.3% for retinal veins. This is in the same range as the reproducibility found in our laboratory with the same instrument. 19 Comparable to the latter results, Hardarson et al. 13 reported SD values for repeated measurements of five images with a four-wavelength system of single vessels of 3.7% in retinal arterioles and 5.3% for retinal veins. Recent evidence suggests that the reproducibility can be further improved up to 1% in arterioles and 1.4% in venules with standardized image acquisition and a newer version of the instrument. 18  
However, although these results indicate good reproducibility, the validity of measurements still needs to be proven. In particular, the question whether the measurements truly reflect oxygen saturation is difficult to resolve because no gold-standard method for the measurement of retinal oxygen saturation in humans exists. Several attempts have been made to test the validity of the measurements. As such, it has been shown that measured arteriolar oxygen saturation is associated with changes in inspired oxygen concentration as induced by breathing pure oxygen. This approach, however, is limited by the fact that healthy subjects even under ambient air conditions show almost saturated hemoglobin in retinal arteries. In addition, in an in vitro study blood samples in glass capillaries were placed in an artificial eye to determine oxygen concentration. The results of the study indicate reasonable agreement between the measured oxygen saturation values in the glass capillaries and those calculated by the oximetry model, even if the background reflectance of the model eye was changed. 20 Although the oximetry model used in the previously mentioned study differs from the model used in the Imedos instrument, it indicates the potential ability of such an instrumental setting to reflect the true oxygen concentration. 
In contrast to hyperoxia, a hypoxia model is more difficult to induce in humans. In a recent study, it was demonstrated that in patients with Eisenmenger syndrome, a cyanotic cardiac defect, retinal arterial oxygen saturation was lower compared with that in healthy subjects. 21 In our approach, we set out to measure oxygen tension in patients with chronic hypoxia with and without additional oxygen supplementation. All patients under study used a portable oxygen concentrator for the sustained delivery of highly concentrated oxygen. Using the oxygen concentrator device, patients who are chronically hypoxic without therapy can be shifted to normoxic arterial oxygen saturation values. This is also reflected in our results, indicating that oxygen partial pressure increases from approximately 60 mm Hg to approximately 80 mm Hg due to the use of the oxygen concentrator. Long-term use of supplemental oxygen has been shown to improve survival in patients with COPD and severe resting hypoxemia. 22  
As shown by the correlation analysis and the Bland–Altman plot, our results demonstrate a strong agreement between oxygen saturation as measured in retinal arteries and the peripheral arterial oxygen saturation as determined by the pulse oximeter. The line of unity lies within the confidence interval in the correlation analysis supporting the validity of the measurement. Good agreement was also found between retinal arterial oxygen saturation and the peripheral arterial oxygen saturation as measured from the earlobe. In addition, the change in arterial oxygen saturation in the retinal vessels strongly correlated with the changes in arterial oxygen saturation seen in the peripheral blood. Given that this relative value is more stable against individual physiologic differences than the absolute values, this again underlies the validity of the technique. The changes in peripheral saturation arterial oxygen saturation, however, were slightly higher than the changes in retinal arterial oxygen saturation. The reasons for this difference are not entirely clear but may be related to the different vascular beds in which oxygen saturation was measured. In addition, differences in local blood flow and blood flow regulation in response to changes in oxygen saturation may also contribute. 
Interestingly, the AV difference did not change after cessation of the oxygen supply. The AV difference as observed in the present study was in the range of 25%. This is slightly smaller than previous observations, which show retinal AV differences of approximately 35% in healthy young volunteers. 9,23 Whether this may be at least partially related to the fact that the patients in the current study were older than those in previous studies is still a matter of controversy, because contradicting evidence exists regarding the effect of age on AV difference. 24,25 In addition, different measurement protocols, in particular the exact place where venous saturation is measured, may also account for the difference. 
Furthermore, our data show that in patients with COPD, retinal arterial oxygen saturation is slightly reduced, whereas venous saturation is increased when compared with that of healthy control subjects. The reason for this finding is unclear. However, one could argue that the chronic ischemic nature of the disease may alter ocular hemodynamics and/or blood rheology, which might have an impact on oxygen extraction. However, this issue deserves further investigation and knowledge about ocular blood flow in these patients would be necessary to finally clarify this issue. 
There are several strengths of the present study that require discussion. Importantly, the images were evaluated by an investigator who was not aware of either the diagnosis or the experimental conditions. To the best of our knowledge this is the first study that used masked evaluation of data with noninvasive retinal oxygen saturation measurement. In addition, we have scheduled two identical study days to gain information on the reproducibility, which is a major issue when the technique is applied clinically. 
There are also limitations of our study that have to be mentioned when considering our data. Given that image quality is crucial for the measurement of retinal oxygen saturation, clear optical media are necessary to obtain valid readings. In the current study, one patient had to be excluded from the analysis because of insufficient image quality. In this context, it needs to be mentioned that it is currently not known to what extent changes in optical media, for example, induced by cataract, may influence the measurements. In addition, it is unknown to what extent peripheral arterial oxygen saturation as measured with a pulse oximeter or by analysis of arterial blood samples really reflects the situation in the eye. However, given that the loss of oxygen saturation along the arterial tree is considered to be small, a high degree of association may be expected even if the absolute values differ slightly. 
Finally, although our data indicate that reliable results can be obtained from retinal arteries, they do not necessarily prove that retinal venous data are reliable as well. In addition, as for every other measurement technique, several outliers have been observed in the correlation analysis, and whether this is related to measurement errors from the fundus images, to poor image quality, or to problems with peripheral arterial oxygen saturation is unknown. 
In conclusion, our findings indicate that changes in systemic arterial oxygen saturation as induced by the cessation of oxygen supply to patients with COPD are well reflected in retinal arterial oxygen measurements. In addition, our data show a good correlation between retinal arterial oxygen saturation and peripheral arterial oxygen saturation, indicating good validity of the technique. 
References
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Footnotes
 Disclosure: S. Palkovits, None; M. Lasta, None; A. Boltz, None; D. Schmidl, None; S. Kaya, None; M. Hammer, None; B. Marzluf, None; A. Popa-Cherecheanu, None; S. Frantal, None; L. Schmetterer, None; G. Garhöfer, None
Figure 1. 
 
Retinal oxygen saturation with oxygen supplementation and after cessation of oxygen supplementation on study day 1 (A) and study day 2 (B). Data of both arteries and veins are presented. Box plots indicate mean (open square), median (line), and the 75th and 25th percentiles.
Figure 1. 
 
Retinal oxygen saturation with oxygen supplementation and after cessation of oxygen supplementation on study day 1 (A) and study day 2 (B). Data of both arteries and veins are presented. Box plots indicate mean (open square), median (line), and the 75th and 25th percentiles.
Figure 2. 
 
Correlation between peripheral arterial oxygen saturation as measured with pulse oximetry and oxygen saturation in retinal arteries (r = 0.6, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 2. 
 
Correlation between peripheral arterial oxygen saturation as measured with pulse oximetry and oxygen saturation in retinal arteries (r = 0.6, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 3. 
 
Correlation between peripheral arterial oxygen saturation as measured in capillary blood samples and retinal arterial oxygen saturation (r = 0.54, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 3. 
 
Correlation between peripheral arterial oxygen saturation as measured in capillary blood samples and retinal arterial oxygen saturation (r = 0.54, P < 0.05). Dashed lines indicate 95% confidence intervals; dotted line indicates line of unity.
Figure 4. 
 
Correlation between change in peripheral arterial oxygen saturation as measured with pulse oximetry and change in retinal arterial oxygen saturation (r = 0.53, P < 0.05). Dashed lines indicate 95% confidence intervals.
Figure 4. 
 
Correlation between change in peripheral arterial oxygen saturation as measured with pulse oximetry and change in retinal arterial oxygen saturation (r = 0.53, P < 0.05). Dashed lines indicate 95% confidence intervals.
Figure 5. 
 
Bland–Altman plot comparing data as obtained between peripheral arterial oxygen saturation and retinal arterial oxygen saturation.
Figure 5. 
 
Bland–Altman plot comparing data as obtained between peripheral arterial oxygen saturation and retinal arterial oxygen saturation.
Table. 
 
Baseline Characteristic of the Study Population at the Screening Examination
Table. 
 
Baseline Characteristic of the Study Population at the Screening Examination
Mean ± SD
Age, y 66.6 ± 5.5
SBP, mm Hg 132.5 ± 13.6
DBP, mm Hg 64.1 ± 6.7
MAP, mm Hg 85.9 ± 6.4
HR, bpm 85.9 ± 12.9
SpO2, % 93.8 ± 2.4
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