OCT is commonly used for the evaluation of retinal diseases,13
and other optic neuropathies.30,31
Thus far, OCT has been used to measure the anatomic changes caused by disease. This is the first systematic study that uses OCT to measure a functional change caused by these diseases.
Doppler OCT has previously been used to visualize the two-dimensional17,23
vascular patterns in the retina and choroid. To move beyond visualization and achieve quantitative blood flow measurement, the angle between the flow and the OCT probe beam must be determined. Several methods have been devised to achieve this goal. One approach is to make use of two OCT beams that probe the target from two different angles.33,34
Its drawback is that special hardware is needed; therefore, the method cannot be used with the OCT systems in common clinical use. Another approach is to use a three-dimensional volumetric OCT scan pattern that can be processed to yield the course and orientation of blood vessels.35,36
The limitation of that approach is that a dense volumetric scan of the area around the optic disc requires more than 10 seconds at the speed of current commercially available Fourier-domain OCT systems. This makes measurements susceptible to errors caused by eye motion and variation in flow during the cardiac cycle. To overcome these limitations, we developed the double circular scan pattern that can capture the direction and flow in all retinal vessels six times per second. The method does not require any special hardware and can be implemented on the current generation of Fourier-domain OCT systems.
Our results are largely compatible with previous findings. Retinal blood flow rate and velocity have been shown by several methods to be decreased in glaucoma.37–39
Glaucomatous visual field defects have been correlated with blood flow abnormalities.40
Optic neuropathy is associated with decreased blood flow in the optic nerve head41
as measured by laser Doppler techniques. The PDR subjects in this report had been treated with pan-retinal photocoagulation, which, by destroying retinal tissue, decreases retinal oxygen consumption43
and blood circulation.5
Our method is unique in that vessel flow, velocity, and caliber were rapidly surveyed for the global retinal circulation using a single instrument. In glaucoma, the low flow was associated with low velocity in both arteries and veins, but the vascular cross-sectional areas were comparable to normal. This agreed with previous reports of no differences in retinal vessel diameters between early glaucoma and control subjects.44,45
In NAION and treated PDR, vessel caliber and velocity were both decreased, although the decrease in venous velocity was not statistically significant. The pathophysiological mechanisms for the different patterns of velocity and caliber abnormalities are unclear, and further studies will be needed to validate and explain these findings.
The average measured total venous flow in our study, 47.6 μL/min for 20 normal subjects, was within the range of previously published values—34.0 μL/min7
to 64.9 μL/min8
—determined by laser Doppler velocimetry (LDV). The population SD, 5.4 μL/min, was smaller than that of previous studies, 12.8 μL/min.8
The overall ICC value, 0.85, shows the repeatability is excellent compared with the variation between normal and diseased eyes. We were also encouraged by the high correlation between the Doppler OCT flow measurement and visual field loss in the glaucoma group. These findings may indicate that the Doppler OCT measurements are relatively uncontaminated with measurement errors that could have increased the population SD or obscured correlation with visual function. Accurate measurements could be useful in the diagnosis and staging of glaucoma and in evaluating the effectiveness of new therapies that improve retinal blood flow.
In this study, the volumetric flow rate varied with the vessel diameter with a power coefficient of 2.13 ± 0.08. This is higher than the value of 1.97 in our previous paper,26
though not statistically significant. Our current sample is larger (20 eyes) than our previous study (eight eyes) and likely to be more accurate. This logarithmic slope value is still not as high as the value of 2.8 measured with LDV.7
The lower slope might have resulted from a systematic underestimation of vessel diameter. In a laboratory study, Li et al.46
found that the phase-resolved Doppler OCT algorithm underestimated the diameter of flow profile in a small tube of known diameter. At the edge of the vessel, reflected OCT signal from the stationary vessel wall might have interfered with the Doppler signal from flowing blood within the same beam width. If we added one beam diameter to all our vein diameter measurements, the log-log flow-diameter slope would have been 2.7 and would have agreed better with LDV results and Murray's law.47
We are performing in vitro phantom studies to better characterize these possible measurement biases.
There are several limitations to the double circular scan method. At six circles per second, it is not possible to fully eliminate eye motion and compensate for motion-induced error in the measurement of the Doppler angle. This limits the precision and accuracy of blood flow measurements. Another limitation is that velocity determination is more difficult when the Doppler phase shift is greater than 2π radians between two consecutive axial scans (double phase-wrapping). With the OCT systems used in this study, this can occur in the peak phase of retinal arterial flow, making arterial flow measurements unreliable. Therefore LDV has the advantage of being able to measure both arteries and veins. However, this limitation is not intrinsic. Fourier-domain OCT, with a speed of >200,000 axial scans per second, has been demonstrated using both spectrometric (line-camera)48
approaches. These ultrahigh-speed OCT systems will be able to measure retinal arterial flow and very high blood velocities at large angles without phase wrapping. For average flow velocity calculation, one limitation was that the vessel cross-sectional area was calculated with the assumption that the vessel was round.
Another limitation occurs when the OCT beam is nearly perpendicular to the blood vessels because of the anatomy around the optic nerve head. Measurement in these eyes is possible if the OCT beam can be repositioned in the pupil, changing the angle of approach to the vessel. We must develop a real-time display of the Doppler angle to help the operator adjust the scan angle and to compensate for anomalous anatomic variations. Other subjects in this study could not be measured because of poor vision and poor fixation. Fortunately, most of the subjects in the present study could be measured using current technique and systems.
A final limitation of this technique was the use of a human expert to delineate vascular outlines. To overcome this limitation, we are developing fully automated computer software to identify, delineate, and measure retinal blood vessels. Automated measurement will be needed for widespread clinical use of the Doppler OCT technology.
In summary, we have demonstrated quantitative measurements of total volumetric flow rate, average arterial velocity, average venous velocity, total arterial area, and total venous area in patients with a variety of optic nerve and retinal diseases. Flow deficit correlated well with visual field loss in the optic nerve diseases and with the site of occlusion in BRVO. This is the first systematic application of OCT in the measurement of functional (blood flow) abnormalities instead of anatomic changes in disease. OCT is already a major imaging modality in ophthalmology and is commonly used for retinal diseases and glaucoma evaluation. Our findings could expand the usefulness of OCT in the evaluation of ocular diseases. Larger studies are needed to validate the clinical application of this new technology.