Optical coherence tomography angiography: A comprehensive review of current methods and clinical applications

Abstract

OCT has revolutionized the practice of ophthalmology over the past 10-20 years. Advances in OCT technology have allowed for the creation of novel OCT-based methods. OCT-Angiography (OCTA) is one such method that has rapidly gained clinical acceptance since it was approved by the FDA in late 2016. OCTA images are based on the variable backscattering of light from the vascular and neurosensory tissue in the retina. Since the intensity and phase of backscattered light from retinal tissue varies based on the intrinsic movement of the tissue (e.g. red blood cells are moving, but neurosensory tissue is static), OCTA images are essentially motion-contrast images. This motion-contrast imaging provides reliable, high resolution, and non-invasive images of the retinal vasculature in an efficient manner. In many cases, these images are approaching histology level resolution. This unprecedented resolution coupled with the simple, fast and non-invasive imaging platform have allowed a host of basic and clinical research applications. OCTA demonstrates many important clinical findings including areas of macular telangiectasia, impaired perfusion, microaneurysms, capillary remodeling, some types of intraretinal fluid, and neovascularization among many others. More importantly, OCTA provides depth-resolved information that has never before been available. Correspondingly, OCTA has been used to evaluate a spectrum of retinal vascular diseases including diabetic retinopathy (DR), retinal venous occlusion (RVO), uveitis, retinal arterial occlusion, and age-related macular degeneration among others. In this review, we will discuss the methods used to create OCTA images, the practical applications of OCTA in light of invasive dye-imaging studies (e.g. fluorescein angiography) and review clinical studies demonstrating the utility of OCTA for research and clinical practice.

Keywords: Glaucoma; Macular degeneration; Optical coherence tomography angiography; Physiology; Retina; Vascular disease.

Figure 1

Illustration of OCTA scanning methodology and signal processing scheme. This figure illustrates the theoretical difference in the behavior of OCT beams that interact with retinal tissue depending whether the beams strike blood vessels or neurosensory retinal tissue. At time T1, two OCT beams are incident on the retinal tissue. Beam A1 (red) strikes a retinal artery while beam A2 (blue) strikes adjacent neurosensory retinal tissue that is static. Each beam is back-scattered and generates an A-scan signal shown in the middle. Similarly, at time T2 another scan is performed and illustrated. The interaction of the incident light from beam A1 with moving red blood cells causes more variability in the OCT signal from beam A1 as illustrated in the A-scan signal traces. These signals are then “averaged” as shown by the black arrows to generate a composite OCTA signal that is illustrated in the far right of the panel. The increased variability of the OCT signal from beam A1 is illustrated and is localized to the regions where red blood cell movement occurred. A sample B-scan is illustrated in the lower right of the panel.

Figure 2

Demonstration of various field-of-views in OCTA. (A) 3×3mm² (B) 6×6mm² and (C) 8×8mm² field-of-view pseudocolored OCTA of a normal subject. Red represents superficial retinal layer. Green represents deep retinal layer. Yellow represents regions of overlay. Images are from an AngioPlex^™ device (Carl Zeiss Meditec).

Figure 3

Curvelet-based denoising of OCTA from a normal control (the first row, A–C) and from a patient with diabetic retinopathy (the second row, D–F). The color-coded en face maximum intensity projection of the superficial layer are shown to demonstrate the 3D depth of the retinal vasculature for the original (the first column, A and C) and denoised (the second column, B and E) OCTA. Non-color coded, volume rendered and denoised OCTA using 3D Slicer are shown in the third column (C,F). Color coding in first two columns represents the depth of retinal vessels within the displayed data set for the superficial retinal layer. (Red represents the most superficial, green deeper and blue the deepest capillaries within the superifical retinal layer that is shown). Note that only the superficial retinal layer is shown in this data set so the color coding does not correspond to that in other figures.

Figure 4

Fluorescein angiogram and corresponding OCT and OCTA images of subject with mild-moderate nonproliferative diabetic retinopathy on clinical exam. (A) Fluorescein angiogram in the late phase shows an area of hypofluorescence that is consistent with impaired perfusion. The white dotted lines represent the area of the FA shown in the OCTA image in the last panel. (B1) An B-scan from the OCTA dataset through the superior macula showing a small area of intraretinal fluid. (B2) An B-scan through the fovea. (C) OCTA corresponding to the area of the white-dotted box in panel (A). There are clear areas of impaired perfusion on the OCTA. The dotted lines represent the location of the B-scans in panel B.

Figure 5

OCTA of subject with proliferative diabetic retinopathy and neovascularization of the disc. (A) Depth encoded OCTA of optic nerve head demonstrates a significant area of superifical (red) OCTA signal corresponding to the neovascularziation above the disc on the (B) B-scan. Red represents superficial retinal layer. In this case the neovascularization is red because it is in the vitreous and above the superficial retinal layer. Green represents DRL. Yellow represents regions of overlay.

Figure 6

Images from a subject with severe nonproliferative diabetic retinopathy and macular edema. (A) Color fundus image shows diffuse areas of hard exudate and intraretinal hemorrhage. (B) Fluorescein angiogram shows numerous microaneurysms but no clear leakage or diabetic macular edema in mid to late frames. (C) OCTA of the central 3×3mm² shows irregularities in the capillary network and foveal avascular zone as well as an area of increased OCTA signal covering the majority of the fovea (red). This area corresponds to the area of hyperreflective cystoid change seen in (D) B-scan cross section through the fovea. Note the hard exudates on the OCT B-scan. The appearance of the OCTA hyperreflectivity is subjectively correlated with presence of hard exudates in at least some cases and referred to as small scattering particles in motion or SPPiM

Figure 7

Images from an asymptomatic subject with minimal nonproliferative diabetic retinopathy and 20/20 vision. (A) Color fundus photograph, (B) Depth-encoded OCTA shows an irregular foveal avascular zone and some pockets of mild impaired capillary perfusion in the periphery of the images. These findings were not visible on clinical exam or other imaging modalities. (C) B-scan through the fovea shows no intraretinal fluid.

Figure 8

OCTA of a 36 year old female with a chronic (>1 year) retinal vascular occlusion and inner retinal atrophy involving the superior macula but sparing the fovea. (A) Depth encoded pseudocolored map of the superficial and mid-retinal vasculature. Red = superficial vasculature. Green = middle retinal vasculature. Yellow = red/green overlay. (B) Raw OCTA intensity image of superficial layer demonstrates lack of superficial blood flow in most of the superior half of the macula and apparent decreased vascular density in most of superior retina. (C) Raw OCTA intensity image of mid-retinal vasculature demonstrates similar extensive loss of blood flow characteristic of the mid-retinal layer in superior macula. The OCTA signal from the larger retinal vessels in the superior macula are not characteristic of the mid-retinal layer and appear here because of the atrophy of the inner retina and displacement of the larger retinal vessels deeper into the retina as shown in the B-scans below. (E–H) Segmentation of corresponding layers shown in the B-scan at the level of the fine blue line in above images.

Figure 9

En face SD-OCTA images of the superficial retinal slab from (A) normal subject and (B) patient’s left eye demonstrates an inferotemporal perfusion defect consistent with inferotemporal glaucomatous damage.

Figure 10

OCTA of subjects with various types of choroidal neovascularization (CNV). (A1–4) Type 1 macular neovascularization. (A1) The CNV is shown by the en face OCTA slab with the inner boundary as the retinal pigment epithelium (RPE) line and the outer boundary as the RPE-fit line (Bruch’s membrane). (A2) The en face structural image shows intensity variations within the slab. (A3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the lesion is located below the RPE and above Bruch’s membrane. (B1–4) Type 2 macular neovascularization. (B1) The CNV is shown by the en face OCTA slab with the inner boundary defined by from the outer plexiform layer and the outer boundary located at 37 μm under Bruch’s membrane. (B2) The en face structural image shows intensity variations within the slab. (B3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the lesion is located above the RPE. (C1–4) Type 3 macular neovascularization (retinal angiomatous proliferation). (C1) Depth encoded en face OCTA slab shows a bright green focal lesion just superior to the fovea. There are focal areas with a poorly defined flow signal that represent suspended scattering particles in motion (SSPiM) associated with cystic intraretinal cavities (arrow). (C2) The en face structural image demonstrates hyporeflective cystic spaces consistent with the intraretinal fluid. (C3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the neovascular flow lesion is located within the retina along with areas of SSPIM.

Figure 11

Subject with microscopic polyangitis and macular edema. (A) Depth encoded OCTA shows diffuse and severe vascular changes in the superior macula. There are focal dilatations of the capillaries and regions of microaneurysmal changes. (B) Superficial retinal layer and (C) DRL slabs shown separately for clarity. (D) B-scan through the fovea from OCTA dataset shows macular edema.

Figure 12

Spectral Domain OCTA of subjects with various stages of macular telangiectasia type 2 (MacTel2). (A1–4) Early non-proliferative MacTel2. (A1) Depth encoded en face retina flow image of the left eye shows the early subtle changes of retina microvasculature temporal to the fovea. The depth-encoded color flow image of the retinal layers depicts the superficial capillary plexus as red, the deep capillary plexus as green, and the avascular retina as blue. Due to this color-coding, it’s possible to appreciate that the early change of retina vessels begin from the deep retina. (A2) The en face intensity image shows intra-retinal cysts that appear as areas of decreased reflectivity (arrow). (A3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the cystic cavity with drapping of the internal limiting membrane can be appreciated on cross-sectional B-scan and correspond to the areas of decreased reflectivity seen on the en face image. (B1–4) Intermediate non-proliferative MacTel2. (B1) Depth encoded en face retina flow image of the left eye shows the the abnormal microvasculature involving all the parafoveal retinal plexuses. (B2) The en face intensity image shows intra-retinal areas of decreased reflectivity corresponding to intraretinal cavities (arrow). (B3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the retinal cavity can be appreciated along with disruption of the photoreceptor inner-–outer-segment band (ellipsoid zone). (C1–4) Proliferative MacTel2. (C1) Depth encoded en face retina flow image of the left eye showing anastomosis between the superficial and deep retina vessels and a proliferative tangle corresponding to the neovascularization. (C2) The en face intensity image shows intra-retinal areas of decreased reflectivity corresponding to an intraretinal cavity (arrow). (C3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the thickening of retina temporal to the fovea and the dilated microvasculature. (D1–4) Same subject with proliferative MacTel2 as in C, but the outer retinal slab is selected, which is normally an avascular layer. (D1) Outer retinal en face flow image of the left eye with projection artifact removal showing the neovascularization. (D2) The en face intensity image showing the shadows from the superficial retinal vasculature. (D3–4) Corresponding B-scans with the slab segmentations lines, with and without the flow signal. Note that the segmentation lines are located in the outer retina.