July 2016
Volume 57, Issue 9
Open Access
Articles  |   July 2016
Measurement of Retinal Vascular Caliber From Optical Coherence Tomography Phase Images
Author Affiliations & Notes
  • Klemens Fondi
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Gerold C. Aschinger
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
    Institute of Applied Physics, Vienna University of Technology, Vienna, Austria
  • Ahmed M. Bata
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Piotr A. Wozniak
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Liang Liao
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Gerald Seidel
    Department of Ophthalmology, Medical University of Graz, Graz, Austria
  • Veronika Doblhoff-Dier
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
    Institute of Applied Physics, Vienna University of Technology, Vienna, Austria
  • Doreen Schmidl
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Gerhard Garhöfer
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • René M. Werkmeister
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  • Leopold Schmetterer
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
    Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  • Correspondence: Leopold Schmetterer, Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; leopold.schmetterer@meduniwien.ac.at
Investigative Ophthalmology & Visual Science July 2016, Vol.57, OCT121-OCT129. doi:10.1167/iovs.15-18476
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Klemens Fondi, Gerold C. Aschinger, Ahmed M. Bata, Piotr A. Wozniak, Liang Liao, Gerald Seidel, Veronika Doblhoff-Dier, Doreen Schmidl, Gerhard Garhöfer, René M. Werkmeister, Leopold Schmetterer; Measurement of Retinal Vascular Caliber From Optical Coherence Tomography Phase Images. Invest. Ophthalmol. Vis. Sci. 2016;57(9):OCT121-OCT129. doi: 10.1167/iovs.15-18476.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: To compare retinal vessel calibers extracted from phase-sensitive optical coherence tomography (OCT) images with vessel calibers as obtained from the Retinal Vessel Analyzer (RVA).

Methods: Data from previously published studies in 13 healthy subjects breathing room air (n = 214 vessels) and 7 subjects breathing 100% oxygen (n = 101 vessels) were used. Vessel calibers from OCT phase images were measured vertically along the optical axis by three independent graders. The data from RVA fundus images were corrected for magnification to obtain absolute values.

Results: The average vessel diameter as obtained from OCT images during normoxia was lower than from RVA images (83.8 ± 28.2 μm versus 86.6 ± 28.0 μm, P < 0.001). The same phenomenon was observed during 100% oxygen breathing (OCT: 81.0 ± 22.4 μm, RVA: 85.5 ± 26.0 μm; P = 0.001). Although the agreement between the two methods was generally high, the difference in individual vessels could be as high as 40%. These differences were neither dependent on absolute vessel size nor preferably found in specific subjects. Interobserver differences between OCT evaluators were much lower than differences between the techniques.

Conclusions: Extracting vessel calibers from OCT phase images may be an attractive approach to overcome some of the problems associated with fundus imaging. The source of differences in vessel caliber between the two methods remains to be investigated. In addition, it remains unclear whether OCT-based vessel caliber measurement is superior to fundus camera–based imaging in risk stratification for systemic or ocular disease. (ClinicalTrials.gov numbers, NCT00914407, NCT02531399.)

Retinal vascular calibers are usually measured from fundus photographs using digital imaging.1 Most approaches nowadays follow the formula developed by Hubbard and coworkers1 to calculate the central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE). The dimensionless quotient arteriovenous ratio (AVR) is used in most studies because it is independent of the magnification of the image, which depends on both the optics of the fundus camera and the optical properties of the eye.1 
Because abnormalities in retinal vascular calibers are associated with a wide variety of cardiovascular, ocular, kidney, and brain diseases, accurate measurement of retinal vascular calibers is desired.2 However, some limitations of the currently available technology prevent the translation of such measurement into clinical praxis: the absolute measurement of vessel caliber is not possible, measurements are usually done from one fundus image only and recorded at an undefined time point during the cardiac cycle, pupil dilatation is required, and the three-dimensional geometry of the vessel is not taken into account.2,3 
A potential approach to overcome these problems is to use optical coherence tomography (OCT). This technique offers the advantage of easier recording, provides three-dimensional information, and is, at least in depth, independent of magnification problems. The measurement of vascular caliber data from OCT images is, however, not straightforward. In OCT, larger retinal vessels cause a characteristic shadowing effect that is caused by the scattering of light at red blood cells (RBCs). Extraction of data can be done either vertically along the axis of the illuminating beam or horizontally in the retinal plane. In this context, it needs to be considered that the resolution of typical commercially available OCT systems is in the order of 5 μm vertically and 15 to 20 μm horizontally.4 In larger vessels, a characteristic shadowing effect caused by the scattering of light at RBCs can impair accurate vessel delineation. It follows that several different approaches were published to extract caliber data from retinal vessels based on OCT.58 
In the present study, we set out to measure retinal vascular caliber from the phase values of the complex OCT signal. More than a decade ago, it was shown that extraction of the phase from Fourier-domain OCT (FD-OCT) images can be used to contrast blood vessels.9,10 Nowadays these techniques are widely used in OCT angiography and also form the basis for quantitative blood flow measurement.11 This approach was used in the present study to measure vessel diameters and then compare them to the measurements of vessel calibers from fundus images in healthy subjects. 
Methods
Subjects
The data in the present report were obtained from one yet unpublished study and two studies that were published previously.12,13 The studies were undertaken to measure total retinal blood flow and total retinal oxygen extraction in healthy subjects. The study protocols were approved by the Ethics Committee of the Medical University of Vienna and followed the guidelines set forth in the Declaration of Helsinki. All subjects passed a screening examination before the study day that included a physical examination, blood sampling to assess hematologic status and chemistry, a 12-lead electrocardiogram, the measurement of visual acuity, slit lamp biomicroscopy, funduscopy, and the measurement of IOP. Exclusion criteria were ametropia ≥3 diopters, anisometropia ≥3 diopters, other ocular abnormalities, and any clinically relevant illness as judged by the investigators, as well as a blood donation or intake of any medication in the 3 weeks before the study. The participants had to abstain from beverages containing alcohol or caffeine in the 12 hours before the study visit. 
Protocol
The measurements were conducted under dilated pupil conditions using a custom-built dual-beam bidirectional Doppler FD-OCT to measure phase shifts and a Retinal Vessel Analyzer (RVA; Imedos Systems UG, Jena, Germany) to quantify vessel calibers.12,13 Subjects were measured while breathing ambient air (n = 13) or 100% oxygen (n = 7, gases for human use; Messer, Vienna, Austria), which was delivered via a partially expanded reservoir bag at atmospheric pressure. The phase of inhaling 100% oxygen lasted 30 minutes and measurements began 15 minutes after the start of the inhalation. 
Extraction of Retinal Calibers From OCT Phase Images
The measurements were performed with a dual-beam Doppler FD-OCT system as described in detail previously.12,14,15 Briefly, two orthogonally polarized probe beams under a known angle Δα are used to illuminate the fundus. The system records the spectra of the two channels as a function of frequency using two identical spectrometers. When the beams fall onto blood vessels, the back-reflected light in each channel is Doppler-shifted because of the movement of the RBCs. We have shown that with such a setup it is possible to measure absolute blood flow in particular retinal vessels14 as well as total retinal blood flow.12 The refractive index of blood (1.37) at the used light source's wavelength was included in the calculations.14 In the current study, we extracted retinal calibers from these measurements (Fig. 1). A total of 60 frames were recorded for each vessel during a measurement period of 5 seconds. Hence, our observation time was longer than one cardiac cycle. Frames 0, 10, 20, 30, 40, 50, and 59 of each recording were evaluated, resulting in a total of seven diameter readings for each vessel. In each of these images, the areas with phase shifts caused by the moving RBCs were evaluated, using the phase image from the channel that showed better phase contrast between moving RBCs and static tissue. The outer border of the phase-shifted areas was determined manually by three independent observers (KF, AMB, LL). The retinal vessel diameter as obtained from the OCT phase images was defined as the mean of those seven measurements. 
Figure 1
 
Sample measurement in a healthy subject. Fundus image (A) and OCT phase image (B) are acquired at the same position. Data from fundus images are obtained within the retinal plane, data from phase OCT images are obtained from the depth profile, because OCT provides better resolution in depth than transversally.
Figure 1
 
Sample measurement in a healthy subject. Fundus image (A) and OCT phase image (B) are acquired at the same position. Data from fundus images are obtained within the retinal plane, data from phase OCT images are obtained from the depth profile, because OCT provides better resolution in depth than transversally.
Extraction of Retinal Calibers From Fundus Images
The OCT setup is integrated into a commercially available RVA (Imedos Systems UG), and the details of this coupling were recently reported.12 Imaging with the RVA is done via a fundus camera (FF450plus; Carl Zeiss Meditec AG, Jena, Germany) and a charge-coupled device camera allowing for the measurement of retinal vessel diameters. The principle of measurement of vessel diameters with this technique is essentially a measurement of the width of the RBC column inside the vessels.3,16 In the present study, we used a prototype analyzing software provided by Imedos, which allows for calculation of absolute values in micrometers based on the individual axial eye length, the axial refraction for each subject, and the optical characteristics of the fundus camera system. This software was already used in our previous studies.12,13 
Statistical Analysis
From our data, CRAE, CRVE, as well as AVR were calculated. This was done by using the formula developed by Hubbard and coworkers,1 in the revised version of Knudtson et al.17 As explained above, the retinal vessel diameters from the OCT measurements were calculated as the means obtained by the three evaluators. Retinal vessel diameter data were then compared between the two methods that we used. Several types of analysis were performed. Paired t-tests were used to calculate significant differences between the two techniques. In addition, we prepared Bland-Altman plots and plotted the frequency of relative differences. Linear correlation analysis was done for each subject individually. Furthermore, we analyzed the differences among the three evaluators of the OCT data by linear correlation analysis. Data during ambient room air breathing and 100% oxygen breathing were calculated separately. A P value less than 0.05 was considered statistically significant. All statistical analysis was done with SPSS Version 22 (IBM SPSS Statistics, Armonk, NY, USA). 
Results
A total of 214 retinal vessels were evaluated under breathing room air. The average vessel diameter in OCT images was 83.8 ± 28.2 μm; the average vessel diameter in RVA images was 86.6 ± 28.0 μm. The difference of 2.8 ± 10.7 μm was statistically significant (P < 0.001). During 100% oxygen breathing, a total of 101 vessels were evaluated. Again, the retinal vessel diameters were smaller when evaluated using OCT (81.0 ± 22.4 μm) as compared with RVA (85.5 ± 26.0 μm; t-test P = 0.001). Bland-Altman plots for comparing OCT and RVA data are presented in Figure 2. The data are presented separately for arteries and veins. As evidenced also from t-test analysis, data were slightly higher when measured with RVA, although the difference is small. In some cases, however, considerable differences were found between RVA and OCT data. These deviations were as high as 40% and seen equally in arteries and veins. This is also shown in the graphs summarizing the frequencies of relative differences between the two measuring methods (Fig. 3). During normoxia, 61.9% of the retinal arteries and 66.3% of the retinal veins were larger when measured with RVA than OCT. During hyperoxia, 62.3% and 66.7% of retinal arteries and retinal veins, respectively, were larger when measured with the RVA than with OCT, respectively. 
Figure 2
 
Bland-Altman plots comparing retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately. On the x-axis, the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 2
 
Bland-Altman plots comparing retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately. On the x-axis, the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 3
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately.
Figure 3
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately.
In Figures 4 and 5, the individual correlations for retinal arteries and retinal veins are presented during normoxia and hyperoxia, respectively. Correlations were generally high, and the regression line was close to 45 degrees. For retinal veins during normoxia, the deviations from regression line slopes of 1 were small. Only one case (subject 8) showed a slope of regression line of 0.46 during breathing room air. This subject's correlation in the retinal arteries was, however, good. 
Figure 4
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during breathing room air. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 4
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during breathing room air. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 5
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during 100% oxygen breathing. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 5
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during 100% oxygen breathing. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 6 presents the relative differences between OCT and RVA data for each investigator separately. The data indicate that the RVA values were always higher than OCT values independently of the evaluator. The differences between the evaluators were considerably smaller than the differences between the methods. 
Figure 6
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA presented for each evaluator separately. Data are presented during both breathing room air and 100% oxygen.
Figure 6
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA presented for each evaluator separately. Data are presented during both breathing room air and 100% oxygen.
Figure 7 shows the linear regression analysis for the data obtained by the three investigators. During normoxia, the correlation was high (correlation coefficients between 0.95 and 0.96) with the slope of regression lines close to 1 (between 0.99 and 1.01). During hyperoxia, the slope of regression lines was also close to 1 (between 0.94 and 0.98) but the correlation was weaker (correlation coefficients between 0.73 and 0.85). 
Figure 7
 
Correlation of retinal vessel diameters as obtained from different evaluators using OCT data. Data are presented during room air and 100% oxygen breathing.
Figure 7
 
Correlation of retinal vessel diameters as obtained from different evaluators using OCT data. Data are presented during room air and 100% oxygen breathing.
Figure 8 compares CRAE, CRVE, and AVR between the two methods. Under normoxia, mean CRAE (154.5 ± 11.9) and CRVE (227.6 ± 17.5) with a mean AVR of 0.68 ± 0.04 calculated from the OCT data were again smaller than the RVA data (CRAE 158.4 ± 13.4, CRVE 231.2 ± 25.4, AVR 0.69 ± 0.06). But these differences did not reach statistical significance (CRAE P = 0.15, CRVE P = 0.46, AVR P = 0.46). Similarly, under hyperoxia, these equivalents were also smaller in the OCT data (CRAE 142.0 ± 11.2, CRVE 195.4 ± 10.9, AVR 0.73 ± 0.06) than in the data from the RVA (CRAE 149.7 ± 11.0, CRVE 211.6 ± 28.5, AVR 0.72 ± 0.09). Also under hyperoxia, these differences did not reach a level of statistical significance (CRAE P = 0.10, CRVE P = 0.08, AVR P = 0.80). 
Figure 8
 
Bland-Altman plots comparing CRAE, CRVE, and AVR as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. On the x-axis the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 8
 
Bland-Altman plots comparing CRAE, CRVE, and AVR as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. On the x-axis the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Discussion
In the present study, we explore the opportunity to measure retinal vascular calibers from OCT phase images. This may be an attractive approach because the contrast between blood vessels and the surrounding tissue is higher in phase than in amplitude images. Our data indicate good agreement between retinal vessel caliber measurements by OCT and caliber measurements on fundus images. Data as obtained with OCT were, however, slightly lower than those obtained with the RVA. In addition, deviations in some individual vessels were relatively high. 
The lower average data as obtained with phase-sensitive OCT may be caused by the phase noise of the OCT system. Whereas in fundus imaging the vessel caliber is defined by the column of the RBCs,3 in phase-sensitive OCT, the caliber information is extracted from the velocity data. Very low velocities close to the vessel wall may therefore be missed with the OCT technology because of the phase noise of the system. In our measurements, we minimize this problem by using oversampling,15,18 but still the diameter may be underestimated accordingly. Alternatively, it also may be that vessel diameters as obtained from fundus images in the present study are too large. This could, for instance, result from imperfect focusing of the retinal plane during RVA measurements, although care was taken to obtain optimal image quality. Moreover, one has to consider that the shape of the vessel is not necessarily circular and that RVA and OCT, as used in the present study, measure horizontal and vertical diameters, respectively. If such a phenomenon exists, it should, however, be more pronounced in veins than in arteries because of the lower transmural pressure. 
In the absence of a true gold standard technology for measuring absolute vessel diameters, it is difficult to answer which of the examined techniques shows better validity. As shown in Figures 2 and 3, the values obtained by the two techniques can in some vessels differ considerably. The reasons for these differences are not clear. The Bland-Altman plots presented in Figure 2 indicate that this is not more frequently found in vessels of smaller calibers. This would be the case if phase noise would be responsible, because there is a linear correlation between velocity and diameter in retinal vessels.19,20 The data presented in Figures 4 and 5 indicate that the differences between the methods are not primarily found in selected subjects, but rather are observed in individual vessels of some subjects. This also indicates that magnification problems with the RVA are not the primary source of these differences. Finally, Figure 7 indicates that the main difference between the RVA and OCT is not due to grader differences, because agreement between evaluators was much higher than between OCT and RVA (see also Fig. 6). 
Interestingly, the data presented in Figure 7 indicate that there was better agreement between observers during normoxia than during hyperoxia. It is well established that during 100% oxygen breathing, retinal vessels show pronounced vasoconstriction associated with a pronounced reduction in retinal blood flow and retinal oxygen extraction.13,2125 As such, our data might indicate that the interobserver variability is less pronounced in larger than in smaller vessels. To which degree an automated measurement of vessel diameters from phase images would reduce the difference between RVA and OCT data remains to be investigated. 
In the present study, we used images as obtained with a bidirectional Doppler OCT system to extract vessel caliber data. This system was originally developed for measuring total retinal blood flow12 and for extracting three-dimensional velocity profiles.26 For the present application, this has the advantage that two images were available, of which the one with the better contrast could be chosen for evaluation. Furthermore, with this OCT system, images were recorded over a certain period of time, providing representative mean vessel caliber values, whereas fundus images are taken with the RVA at a single undefined time point during the cardiac cycle.3,12 Other investigators used faster Doppler OCT systems for measuring retinal blood flow either using B-scans or enface images.2731 How the diameter data as obtained with such technologies compares with fundus camera–based imaging remains to be investigated. 
A wide variety of large-scale studies have looked into the association between retinal vascular calibers and disease. Among others, clear associations with altered retinal vascular diameters were shown for incident stroke,32,33 systemic hypertension,34 diabetic retinopathy,35 and glaucoma.36 In these studies, CRAE, CRVE, or AVR were used for risk assessment. Figure 8 indicates that CRAE, CRVE, and AVR may significantly differ if taken from either OCT or RVA. How OCT and fundus imaging data compare in risk assessment is therefore unknown. In addition, it remains to be established whether the measurement of absolute vessel caliber offers advantages in this respect. 
In conclusion, the measurement of vessel calibers from OCT data may be an attractive approach for future studies. Further studies are required to better understand the relation between data as obtained from fundus imaging and those extracted from OCT. Extracting phase data from OCT images may, however, overcome some of the limitations of classical fundus imaging and may therefore be an interesting approach for risk stratification in systemic and ocular disease. 
Acknowledgments
Supported by the Austrian Science Foundation (FWF; Projects P26157, KLI250, KLI 283, and KLI340). 
Disclosure: K. Fondi, None; G.C. Aschinger, None; A.M. Bata, None; P.A. Wozniak, None; L. Liao, None; G. Seidel, None; V. Doblhoff-Dier, None; D. Schmidl, None; G. Garhöfer, None; R.M. Werkmeister, None; L. Schmetterer, None 
References
Hubbard LD, Brothers RJ, King WN, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study 1. Ophthalmology. 1999; 106: 2269–2280.
Ikram MK, Ong YT, Cheung CY, Wong TY. Retinal vascular caliber measurements: clinical significance, current knowledge and future perspectives. Ophthalmologica. 2013; 229: 125–136.
Garhofer G, Bek T, Boehm AG, et al. Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol. 2010; 88: 717–722.
Drexler W, Fujimoto JG. State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res. 2008; 27: 45–88.
Goldenberg D, Shahar J, Loewenstein A, Goldstein M. Diameters of retinal blood vessels in a healthy cohort as measured by spectral domain optical coherence tomography. Retina. 2013; 33: 1888–1894.
Muraoka Y, Tsujikawa A, Kumagai K, et al. Age- and hypertension-dependent changes in retinal vessel diameter and wall thickness: an optical coherence tomography study. Am J Ophthalmol. 2013; 156: 706–714.
Schuster AK-G, Fischer JE, Vossmerbaeumer C, Vossmerbaeumer U. Optical coherence tomography-based retinal vessel analysis for the evaluation of hypertensive vasculopathy. Acta Ophthalmol. 2015; 93: e148–153.
Ouyang Y, Shao Q, Scharf D, Joussen AM, Heussen FM. Retinal vessel diameter measurements by spectral domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2015; 253: 499–509.
White B, Pierce M, Nassif N, et al. In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography. Opt Express. 2003; 11: 3490–3497.
Leitgeb R, Schmetterer L, Drexler W, Fercher A, Zawadzki R, Bajraszewski T. Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Opt Express. 2003; 11: 3116–3121.
Leitgeb RA, Werkmeister RM, Blatter C, Schmetterer L. Doppler optical coherence tomography. Prog Retin Eye Res. 2014; 41: 26–43.
Doblhoff-Dier V, Schmetterer L, Vilser W, et al. Measurement of the total retinal blood flow using dual beam Fourier-domain Doppler optical coherence tomography with orthogonal detection planes. Biomed Opt Express. 2014; 5: 630–642.
Werkmeister RM, Schmidl D, Aschinger G, et al. Retinal oxygen extraction in humans. Sci Rep. 2015; 5: 15763.
Werkmeister RM, Dragostinoff N, Pircher M, et al. Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels. Opt Lett. 2008; 33: 2967–2969.
Werkmeister RM, Dragostinoff N, Palkovits S, et al. Measurement of absolute blood flow velocity and blood flow in the human retina by dual-beam bidirectional Doppler Fourier-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2012; 53: 6062–6071.
Vilser W, Nagel E, Lanzl I. Retinal vessel analysis—new possibilities. Biomed Tech (Berl). 2002; 47: 682–685.
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BE. Revised formulas for summarizing retinal vessel diameters. Curr Eye Res. 2003; 27: 143–149.
Werkmeister RM, Palkovits S, Told R, et al. Response of retinal blood flow to systemic hyperoxia as measured with dual-beam bidirectional Doppler Fourier-domain optical coherence tomography. PLoS One. 2012; 7: e45876.
Riva CE, Grunwald JE, Sinclair SH, Petrig BL. Blood velocity and volumetric flow rate in human retinal vessels. Invest Ophthalmol Vis Sci. 1985; 26: 1124–1132.
Garhofer G, Werkmeister R, Dragostinoff N, Schmetterer L. Retinal blood flow in healthy young subjects. Invest Ophthalmol Vis Sci. 2012; 53: 698–703.
Grunwald JE, Riva CE, Brucker AJ, Sinclair SH, Petrig BL. Altered retinal vascular response to 100% oxygen breathing in diabetes mellitus. Ophthalmology. 1984; 91: 1447–1452.
Luksch A, Garhöfer G, Imhof A, et al. Effect of inhalation of different mixtures of O(2) and CO(2) on retinal blood flow. Br J Ophthalmol. 2002; 86: 1143–1147.
Kiss B, Polska E, Dorner G, et al. Retinal blood flow during hyperoxia in humans revisited: concerted results using different measurement techniques. Microvasc Res. 2002; 64: 75–85.
Gilmore ED, Hudson C, Venkataraman ST, Preiss D, Fisher J. Comparison of different hyperoxic paradigms to induce vasoconstriction: implications for the investigation of retinal vascular reactivity. Invest Ophthalmol Vis Sci. 2004; 45: 3207–3212.
Gilmore ED, Hudson C, Preiss D, Fisher J. Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation. Am J Physiol Heart Circ Physiol. 2005; 288: H2912–H2917.
Aschinger GC, Schmetterer L, Doblhoff-Dier V, et al. Blood flow velocity vector field reconstruction from dual-beam bidirectional Doppler OCT measurements in retinal veins. Biomed Opt Express. 2015; 6: 1599–1615.
Baumann B, Potsaid B, Kraus MF, et al. Total retinal blood flow measurement with ultrahigh speed swept source/Fourier domain OCT. Biomed Opt Express. 2011; 2: 1539–1552.
Choi W, Baumann B, Liu JJ, et al. Measurement of pulsatile total blood flow in the human and rat retina with ultrahigh speed spectral/Fourier domain OCT. Biomed Opt Express. 2012; 3: 1047–1061.
Srinivasan VJ, Radhakrishnan H. Total average blood flow and angiography in the rat retina. J Biomed Opt. 2013; 18: 76025.
Lee B, Choi W, Liu JJ, et al. Cardiac-gated en face Doppler measurement of retinal blood flow using swept-source optical coherence tomography at 100,000 axial scans per second. Invest Ophthalmol Vis Sci. 2015; 56: 2522–2530.
Tan O, Liu G, Liang L, et al. En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography. J Biomed Opt. 2015; 20: 066004.
Kawasaki R, Xie J, Cheung N, et al. Retinal microvascular signs and risk of stroke: the Multi-Ethnic Study of Atherosclerosis (MESA). Stroke. 2012; 43: 3245–3251.
McGeechan K, Liew G, Macaskill P, et al. Prediction of incident stroke events based on retinal vessel caliber: a systematic review and individual-participant meta-analysis. Am J Epidemiol. 2009; 170: 1323–1332.
Cheung CY, Ikram MK, Sabanayagam C, Wong TY. Retinal microvasculature as a model to study the manifestations of hypertension. Hypertension. 2012; 60: 1094–1103.
Nguyen TT, Wong TY. Retinal vascular changes and diabetic retinopathy. Curr Diab Rep. 2009; 9: 277–283.
Kawasaki R, Wang JJ, Rochtchina E, Lee AJ, Wong TY, Mitchell P. Retinal vessel caliber is associated with the 10-year incidence of glaucoma: the Blue Mountains Eye Study. Ophthalmology. 2013; 120: 84–90.
Figure 1
 
Sample measurement in a healthy subject. Fundus image (A) and OCT phase image (B) are acquired at the same position. Data from fundus images are obtained within the retinal plane, data from phase OCT images are obtained from the depth profile, because OCT provides better resolution in depth than transversally.
Figure 1
 
Sample measurement in a healthy subject. Fundus image (A) and OCT phase image (B) are acquired at the same position. Data from fundus images are obtained within the retinal plane, data from phase OCT images are obtained from the depth profile, because OCT provides better resolution in depth than transversally.
Figure 2
 
Bland-Altman plots comparing retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately. On the x-axis, the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 2
 
Bland-Altman plots comparing retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately. On the x-axis, the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 3
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately.
Figure 3
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. Retinal arteries (red) and retinal veins (blue) are presented separately.
Figure 4
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during breathing room air. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 4
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during breathing room air. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 5
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during 100% oxygen breathing. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 5
 
Correlation of retinal vessel diameters as obtained with OCT and RVA in individual subjects. Data are presented during 100% oxygen breathing. Retinal arteries (red) and retinal veins (blue) are presented in the same graph.
Figure 6
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA presented for each evaluator separately. Data are presented during both breathing room air and 100% oxygen.
Figure 6
 
Relative difference in retinal vessel diameters as obtained with OCT and RVA presented for each evaluator separately. Data are presented during both breathing room air and 100% oxygen.
Figure 7
 
Correlation of retinal vessel diameters as obtained from different evaluators using OCT data. Data are presented during room air and 100% oxygen breathing.
Figure 7
 
Correlation of retinal vessel diameters as obtained from different evaluators using OCT data. Data are presented during room air and 100% oxygen breathing.
Figure 8
 
Bland-Altman plots comparing CRAE, CRVE, and AVR as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. On the x-axis the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
Figure 8
 
Bland-Altman plots comparing CRAE, CRVE, and AVR as obtained with OCT and RVA. Data are presented during both breathing room air and 100% oxygen. On the x-axis the mean value of RVA and OCT data are presented; on the y-axis, the difference between values as obtained with RVA and OCT is shown.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×