Purpose
To evaluate the 3-dimensional architecture of neovascularization in proliferative diabetic retinopathy using Doppler optical coherence tomography (OCT).
Design
Prospective, nonrandomized clinical trial.
Methods
Seventeen eyes of 14 patients with proliferative diabetic retinopathy were prospectively studied. Prototype Doppler OCT was used to evaluate the 3-dimensional vascular architecture at vitreoretinal adhesions.
Results
Proliferative membranes were detected in all eyes with proliferative diabetic retinopathy by standard OCT images. Doppler OCT images detected blood flow by neovascularization of the disc in 12 eyes and neovascularization elsewhere in 11 eyes. Doppler OCT images showed the 3-dimensional extent of new vessels at various stages of neovascularization, and the extent of new vessels could be clearly confirmed at vitreoretinal adhesions.
Conclusions
Doppler OCT is useful for the detection and evaluation of the 3-dimensional vascular structure of neovascularization, and can assist in the noninvasive assessment of proliferative diabetic retinopathy.
Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. Neovascularization of the disc and neovascularization elsewhere are characteristic findings of PDR, and cause vitreous hemorrhage and tractional retinal detachment. Proper evaluation of neovascularization is therefore crucial for the diagnosis and treatment of this disorder. In current clinical practice, color fundus photography and biomicroscopy are basic techniques used to evaluate neovascularization; however, these techniques have limited ability to detect the early stages of new vessel development. Fluorescein angiography is a powerful technique to detect the early stages of new vessels. However, clinical applications of fluorescein angiography have been limited because of the remote possibility of severe complications. Furthermore, limited axial resolution of fluorescein angiography has impeded the evaluation of the 3-dimensional structure of the new vessels.
Optical coherence tomography (OCT) is a noninvasive method that can achieve micrometer-level axial resolution in cross-sectional images of the retina. OCT has provided important information about the 3-dimensional structure of the neovascular complex in PDR. However, standard OCT is only sensitive to backscattering light intensity, and cannot provide information about blood flow. Because of this limitation, standard OCT has a limited ability to evaluate neovascularization. Doppler OCT is a functional extension of OCT technology that is capable of Doppler shifts arising from blood flow. It can provide 3-dimensional vascular images with micrometer-level axial resolution in cross-sectional images of the retina. The clinical utility of Doppler OCT in evaluating the 3-dimensional vascular architecture of choroidal new vessels has already been reported. It is therefore possible that Doppler OCT can facilitate a more comprehensive evaluation of retinal neovascularization in PDR. In this study, we present the clinical application of Doppler OCT for characterization of PDR, and describe the 3-dimensional vascular architecture at the site of neovascularization.
Methods
This prospective, nonrandomized study was performed according to the tenets of the Declaration of Helsinki, and was prospectively approved by the Institutional Review Boards of the University of Tsukuba and Tokyo Medical University. The nature of the current study and the implications of participating in this research were explained to all study candidates, after which a written informed consent was obtained from each participant before any study procedures or examinations were performed.
As controls, we examined 8 eyes of 8 healthy Japanese volunteers (4 men and 4 women; age range, 27–53 years; mean age, 36.1 years). For PDR cases, we evaluated 17 eyes of 14 Japanese patients with PDR ( Table ; 10 men, 4 women; age range, 30–72 years; mean age, 51.5 years). Eyes with severe cataracts or other eye diseases that interfered with Doppler OCT image quality were excluded from this study. The clinical diagnosis of PDR was made by color fundus photography or fluorescein angiography. Four patients had type 1 diabetes and 10 patients had type 2 diabetes. The average hemoglobin A1C in all enrolled patients was 8.6% (range, 6.3%–13.9%). The left eye of Subject 3 was diagnosed as early-stage preproliferative diabetic retinopathy and was evaluated for comparison.
| Subject | Age (y) | Sex | HBA1c (%) | Type of Diabetes | Eye | Neovascular Complex | Figure |
|---|---|---|---|---|---|---|---|
| 1 | 61 | M | 9.7 | 2 | OD | NVD | |
| OS | NVD, NVE | 2 | |||||
| 2 | 45 | F | 9.9 | 1 | OD | NVD, NVE | 3,6 |
| 3 | 48 | M | 6.3 | 1 | OD | NVE | 5 |
| 4 | 55 | M | 6.5 | 2 | OD | NVD, NVE | 7 |
| 5 | 57 | M | 10.4 | 2 | OS | NVD | |
| 6 | 50 | F | 6.6 | 2 | OD | NVE | |
| 7 | 51 | F | 10.3 | 2 | OD | NVD, NVE | |
| OS | NVD, NVE | ||||||
| 8 | 39 | M | 10.3 | 1 | OS | NVD | |
| 9 | 66 | M | 8 | 2 | OD | NVD | |
| OS | NVD, NVE | ||||||
| 10 | 70 | M | 9.1 | 2 | OS | NVD | |
| 11 | 72 | F | 9 | 2 | OD | NVE | |
| 12 | 30 | M | 13.9 | 1 | OS | NVE | |
| 13 | 65 | M | 6.5 | 2 | OD | NVE | |
| 14 | 39 | M | 7.2 | 2 | OS | NVD |
A detailed description of the prototype Doppler OCT system, built by the Computational Optic Group at the University of Tsukuba, has been previously reported. This Doppler OCT was based on a swept-source technology, and operated at an axial scan speed of 100 000 A-scans/s, using a swept-source laser at a central wavelength of 1060 nm. The axial resolution for the tissue in this study was 6.4 μm. In a single scan, the system simultaneously provided both an intensity-based standard OCT image and a Doppler OCT image. The Doppler signal was calculated from 2 A-lines in 2 successive B-scans. Doppler signals were displayed in the form of the squared energy of the Doppler phase shift. Raster scanning protocol with 256 A-lines × 2048 B-scans covering a 6.0 × 6.0-mm region on the retina was used for volumetric scans. In 1 eye (Subject 4), raster scanning protocol with 256 A-lines × 2048 B-scans covering a 3.0 × 3.0-mm region on the retina was used to image intraretinal microvascular abnormalities (IRMA). To obtain a clear image of IRMA, the 3-dimensional Doppler OCT volume was automatically segmented to the retina and choroid, and the en face projection Doppler OCT image of the retina was used to localize the IRMA. The acquisition speed of each measurement was 6.6 s/volume.
Results
Normal Eyes
Figure 1 shows Doppler OCT images of a representative 27-year-old healthy subject. The standard OCT image was similar to commercial high-resolution OCT. An en face projection image by standard OCT enabled precise registration of OCT data using color fundus photography. Doppler OCT B-scan images showed the cross-sectional distribution of blood flow in the retina. Composite color Doppler OCT images, in which the Doppler OCT signal was overlaid on the standard OCT with red color, were created from standard OCT and Doppler OCT images to specify the location of blood flow in the standard OCT image. An en face projection image by Doppler OCT clearly showed the chorioretinal vascular architecture.
Early Neovascularization of the Disc
Early neovascularization of the disc involves the neovascular complex within the margin of the optic disc ( Figure 2 ). In 4 eyes, standard OCT and fluorescein angiography confirmed the presence of early neovascularization of the disc. Standard OCT shows a hyperreflective mass at the disc, accompanied by some loop formations. Doppler OCT composite images show the presence of neovascularization throughout the hyperreflective mass. In the early stage of neovascularization of the disc, the presence of neovascularization is often not detected using color fundus photography or biomicroscopy. In contrast, Doppler OCT imaging detected a neovascular complex with the presence of new vessels in the proliferative tissue.
Advanced Neovascularization of the Disc
Ten eyes had advanced neovascularization of the disc. In the advanced stage, neovascular complexes extended beyond the margin of the optic disc and formed vitreoretinal traction ( Figure 3 ). Using standard OCT images, hyperreflective masses became enlarged and covered the optic disc with multiple loop formations, while Doppler OCT showed the presence of new vessels in the hyperreflective neovascular complex.
In the right eye of Subject 2, Doppler OCT composite images showed an increase of new vessels. Using fluorescein angiography images, detailed evaluation of new vessels was impeded by active fluorescein leakages. In contrast, the fine structure of new vessels was clearly detected in Doppler OCT imaging because of its impervious feature to fluorescein leakage ( Figure 3 ). An enlargement of the area of new vessels could be easily identified with a Doppler OCT en face image. In this eye, the neovascular complex was attached to a remnant of the Cloquet canal. Standard OCT could not confirm whether the neovascularization extended into this vitreoretinal traction, while Doppler OCT readily confirmed the absence of blood flow at a remnant of the Cloquet canal.
Figure 4 shows the left eye of Subject 2. Fluorescein angiography images show an early stage of preproliferative diabetic retinopathy without neovascularization of the disc. The standard OCT image shows adhesion of a remnant of the Cloquet canal on the optic disc. An absence of new vessels in this vitreoretinal adhesion was confirmed by a Doppler OCT composite image, illustrating the usefulness of Doppler OCT to confirm the existence of new vessels at vitreoretinal adhesions.
Because of traction to the neovascular complex, tractional retinal detachment developed in 3 eyes. The detached retina lost its architecture, and standard OCT showed tractional retinal detachment and deformed loop formation in the neovascular complex. A Doppler OCT composite image showed the presence of new vessels in the neovascular complex. At the vitreoretinal traction site, new vessels were pulled toward the vitreous, and the amount of displacement could be easily identified by Doppler OCT images ( Supplemental Figure 1 , available at AJO.com ).
Inner Retinal Neovascularization
One eye showed neovascularization in the inner retina ( Figure 5 ). The presence of neovascularization was confirmed by fluorescein angiography. Standard OCT showed a focal hyperreflective mass, located in the inner retinal layers. Focal hyperreflective lesions extended through the inner plexiform layer, ganglion cell layer, and nerve fiber layer. Doppler OCT imaging confirmed the presence of blood flow at neovascularization in this hyperreflective mass.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
