In vivo retinal blood flow measurements were performed on the right eye of the first patient and left eye of the second PDR patient. shows the fundus images of the two subjects. The identified retinal branch veins are labeled. The dashed circles show the scanning positions on the retina.
Fundus images of the patients: (a) diabetic patient without retinopathy; (b) PDR patient. Branch retinal veins are labeled.
and show the sampled Doppler and intensity images of the subjects. In and , the grey signals show the Doppler frequency shift induced by the blood flow within major blood vessels distributed around the optic nerve head. Retinal branch veins are labeled for each subject in both intensity and Doppler images which matching with .
(a) Doppler (View_1) and (b) intensity image (View_2) of the diabetic patient. Retinal branch veins are labeled as 1 to 6.
(a) Doppler (View_3) and (b) intensity image (View_4) of the PDR patient. Retinal branch veins are labeled as 1 to 7.
Due to signal fading in the arterial vessels induced by high flow speed, such as the artery vessel between veins 1 and 2 in , the data analysis was performed on retinal branch veins. The identification of veins among the other vessels distributed around the optic nerve head was based on the flow direction derived from the recorded Doppler frequency shift and the calculated angle between the probe beam and blood vessel [21
]. Knowing the direction of flow can help separate veins from retinal arteries because arteries have a direction of flow towards the retinal periphery from the nerve head, and veins have a direction of flow towards the nerve head from the peripheral retina.
There were eight measurements performed for each subject. Venous blood flow was calculated for each measurement separately. During data processing, if the calculated incidence angle for a single vessel was less than 2.8° from perpendicular, the dataset for that measurement would be rejected to prevent angle error [26
]. Finally, we could get retinal blood flow from five measurements for each subject. The sampled Doppler and OCT images can be seen in the view links in and , in which every eight consequent images are from one measurement. There are total 40 Doppler and 40 intesity images for each subject saved in the OSA ISP file. For images sampled at inner circle r1
, the image size is 900 (horizontal) × 512 (vertical). For images sampled at outher circle r2
, the image size is 1000 (horizontal) × 512 (vertical). The length units in the horizontal and vertical dimensions are 12.56 and 3.7 μm/pixel separately. In Doppler OCT images, the phase value
versus grey scale I is
In order to get total retinal volumetric flow rate, flows from individual branch veins were summed. The calculated total retinal blood flows of each subject were averaged and the coefficient of variation (CV) was calculated. shows the result for the two patients. The first subject (#1) had diabetes but no retinopathy. Her measured total retinal blood flow had a range from 37.4 to 49.2 μl/min. The mean value was 43.3 μl/min, and the standard deviation was 4.4 μl/min. The CV was 10.2%. For the second patient (#2) with PDR, the measured total retinal blood flow had a range from 30.1 to 39.6 μl/min. The mean value was 33.2 μl/min, the standard deviation was 3.7 μl/min and the CV was 11.3%. In , flow data from a normal human group study are also listed as a comparison [28
Total Retinal Blood Flow of Diabetic Subjects
Regional flow distributions of the two patients are shown in . The averaged superior (Fsup
) and inferior flow (Finf
) for the first patient was 21.9 and 21.4 μl/min separately. The flow difference ΔF between superior and inferior was 0.5 μl/min. This value showed there was no big difference comparing the blood flow between superior and inferior retina and her flow distribution was balanced. For the PDR patient, her superior flow was 20.4 μl/min while her inferior flow was 12.8 μl/min. The flow difference between superior and inferior was 7.6 μl/min. Our earlier study [28
] showed a normal value for the blood flow in superior and inferior retina was 23.5 and 22.2 μl/min separately (the last row in ). The inferior blood flow of the second patient was obviously lower than that of normal.
Regional Blood Flow in Diabetic Patients
For the first patient, measured vessel diameter ranged from 59.2 to 133.2 μm. For the second patient, measured vessel diameter ranged from 51.8 to 122.1 μm. To determine the relationship between flow value and vessel diameter, we ploted of F as function of D in log-log scale for the two patients. shows the linear regression result, where the black squares and solid line show the measurement and fitting result from the first patient. The white circles and dashed line show the result for the patient with diabetic retinopathy. For the first patient, the linear regression had a slope of 1.69. The correlation coefficient between vessel diameter and flow was r2=0.97. For the second patient, the slope of the linear regression was 1.39, which was smaller than that of the first patient. The correlation coefficient between vessel diameter and flow was r2=0.46.
Relationship between vessel diameter and blood flow for the two patients: #1: diabetic patient; #2: PDR patient
To compare the flow condition in different vessels, we analyzed the averaged flow velocity Vave for each vein. Vave was calculated with F/S, where S was the vessel cross section area size, S=π(D/2)2. shows the result. For the first patient, Vave had a range from 15.4 to 22.6 mm/s. The mean value was 18.0 mm/s, at a standard deviation of 2.6 mm/s. For the second patient, the averaged velocity had a range from 8.6 to 25.1 mm/s. The mean value was 16.2 mm/s, at a standard deviation of 5.5 mm/s. For the second patient, its averaged flow speed was lower than that of the first one.
Average Flow Velocity in Branch Veins (unit: mm/s)
For each vessel, blood flow velocities were different in the 8 sampled Doppler images due to flow pulsatility. For a single vessel, sampled eight flow velocities were normalized to the maximum one and plotted against time to show the flow pulsation. In , the solid curve shows the flow pulsation for vessel 2 (in ; Diameter 85.1 μm) of the fisrt patient, and the dashed curve shows the flow pulsation for vessel 5 (in ; Diameter 74 μm) of the second patient. There was no big difference observed for the pulsatility for those vessels with similar diameter from two patients.
Flow pulsatility from the two patients: #1: diabetic patient without retinopathy; #2: patient with PDR.
The PDR patient was further examined with fundus photograph and OCT setup (Rtvue; Optovue Inc.). Her fundus image is shown in . Averaged flow velocities for branch veins are labeled. Grey marks in her retina show the surgery treatment history due to retinal damage. It can be seen that more treatments have been done in the lower rim of her inferior retina. This means more damage happened in that area. These damages can correlate with the low blood flow observed in her inferior retinal hemisphere with OCT.
Fundus image of the patient with PDR. Averaged flow velocities for retinal branch veins are labeled (unit, mm/s).
Macular scan was done with Rtvue OCT setup for the PDR patient. shows a three-dimensional image of her macular area. Three-dimensional image set can be found in the view link in . shows her macular thickness measurement result (unit: μm). Based on her macular OCT thickness map, her inferior retina was thinner than her superior retina. In the scanning window, retinal thickness difference between bottom area at inferior side and top area at superior side was more than 20 μm. This means her inferior retina was affected more by retinal disease. Her inferior retinal thickness thinning also matched with flow measurement result, in which her inferior flow is much lower than that of normal people.
OCT test result. (a) Three-dimensional OCT image (View_5); (b) retinal macular thickness map.