A review of optical coherence tomography angiography (OCTA)

Abstract

Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging technique that generates volumetric angiography images in a matter of seconds. This is a nascent technology with a potential wide applicability for retinal vascular disease. At present, level 1 evidence of the technology's clinical applications doesn't exist. In this paper, we introduce the technology, review the available English language publications regarding OCTA, and compare it with the current angiographic gold standards, fluorescein angiography (FA) and indocyanine green angiography (ICGA). Finally we summarize its potential application to retinal vascular diseases. OCTA is quick and non-invasive, and provides volumetric data with the clinical capability of specifically localizing and delineating pathology along with the ability to show both structural and blood flow information in tandem. Its current limitations include a relatively small field of view, inability to show leakage, and proclivity for image artifact due to patient movement/blinking. Published studies hint at OCTA's potential efficacy in the evaluation of common ophthalmologic diseases such age related macular degeneration (AMD), diabetic retinopathy, artery and vein occlusions, and glaucoma. OCTA can detect changes in choroidal blood vessel flow and can elucidate the presence of choroidal neovascularization (CNV) in a variety of conditions but especially in AMD. It provides a highly detailed view of the retinal vasculature, which allows for accurate delineation of the foveal avascular zone (FAZ) in diabetic eyes and detection of subtle microvascular abnormalities in diabetic and vascular occlusive eyes. Optic disc perfusion in glaucomatous eyes is notable as well on OCTA. Further studies are needed to more definitively determine OCTA's utility in the clinical setting and to establish if this technology may offer a non-invasive option of visualizing the retinal vasculature in detail.

Keywords: Age-related macular degeneration; Diabetic retinopathy; Fluorescein angiography; Glaucoma; Indocyanine angiography; Optic disc; Optical coherence tomography angiography; Retina; Retinal vessel occlusion.

Figures

Figure 1

OCTA Wide-Field Montage of a Normal Eye. Optical coherence tomography angiography (OCTA) wide-field montage of the normal right eye of a 56 year old Caucasian man. Images were acquired using the Angiovue software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA) and montaged using Adobe Photoshop (San Jose, CA). This allows for a larger field of view much like fluorescein and indocyanine green angiography while maintaining improved resolution (de Carlo TE et al., unpublished data in review).

Figure 2

OCT Angiogram Fields of View and Segmentation Layers on Angiovue. The normal left eye of a 56 year old Caucasian man using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A) Full-thickness (internal limiting membrane to Bruch’s membrane) 3 x 3 mm OCT angiogram. (B) Full-thickness 6 x 6 mm OCT Angiogram. (C) Full-thickness 8 x 8 mm OCT Angiogram. (D) Fluorescein angiography cropped to approximately 8 x 8 mm or 30 degrees demonstrates less capillary detail than A-C. (E) 3 x 3 mm OCT angiogram of the “Superficial” inner retina. (F) 3 x 3 mm OCT angiogram of the “Deep” inner retina. (G) 3 x 3 mm OCT angiogram of the outer retina shows absence of vasculature. The white represents noise. (H) 3 x 3 mm OCT angiogram of the choriocapillaris is generally homogenous. There is black shadowing from retinal vessels. (I) En-face intensity OCT image. (J) Highly-sampled OCT b-scan image.

Figure 3

OCT Angiogram Fields of View and Segmentation Layers on the SS-OCT Protype. The normal right eye of a 26 year old Caucasian woman using a prototype swept source optical coherence tomography angiography (OCTA) system (Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachussetts Insitute of Technology, Cambridge, MA). (A) Full-thickness (internal limiting membrane to Bruch’s membrane) 3 x 3 mm OCT angiogram. (B) Full-thickness 6 x 6 mm OCT angiogram. (C) Corresponding OCT b-scan. (D) 3 x 3 mm OCT angiogram of the retinal nerve fiber layer plexus of the inner retina. (E) 3 x 3 mm OCT angiogram of the ganglion cell layer plexus of the inner retina. (F) 3 x 3 mm OCT angiogram of the “deep” inner retina.

Figure 4

OCTA and Color Fundus Photo of Drusen in Non-Neovascular AMD. The left eye of a 72 year old Caucasian man with non-neovascular age-related macular degeneration using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A) Color fundus photo zoomed in to an approximately 3 x 3 mm area centered at the macula showing hard and soft drusen. (B) 3 x 3 mm OCT angiogram of the choriocapillaris centered at the macula as in A. The green and red lines represent the x and y axis OCT b-scans respectively which cross at a soft druse demonstrating an area of decreased signal in the choriocapillaris underlying the druse. (C) 3 x 3 mm en-face structural OCT of the choriocapillaris centered at the macula as in A-B. This image was simultaneously obtained during the same scan as the OCT angiogram in B. This structural OCT is still able to show the choriocapillaris changes at the location of the soft drusen in B, but detail is overall limited. (D) Corresponding x axis OCT b-scan at the cross-section demonstrated by the green line in B showing the soft druse. The corresponding OCT b-scans were simultaneously obtained during the same scan as the OCT angiogram in B.

Figure 5

OCTA of Drusen in Non-Neovascular AMD Cases. (A) 3 x 3 mm en-face images of the right eye of a 74 year old Caucasian man with non-neovascular age-related macular degeneration (AMD) using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) En-face structural OCT demonstrating areas of choriocapillaris alteration. (A2-4) OCT angiograms of the choriocapillaris and corresponding x-axis OCT b-scans at the cross-sections shown by the green line of the OCT angiograms. The three soft drusen shown are associated with areas of decreased signal in the choriocapillaris, which could indicate flow impairment. (B) 3 x 3 mm en-face images of the left eye of an 80 year old Asian woman with non-neovascular AMD using the Angiovue OCTA software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (B1) En-face structural OCT demonstrating areas of choriocapillaris changes. (B2-4) OCT angiograms of the choriocapillaris and corresponding x-axis OCT b-scans at the cross-sections shown by the green line of the OCT angiograms. The druse in B2 is not associated with choriocapillaris loss. The other two soft drusen shown correspond to areas of decreased signal in the choriocapillaris, which could indicate flow impairment.

Figure 6

OCTA of GA in Non-Neovascular AMD. 71 year old Caucasian man with geographic atrophy (GA) due to non-neovascular age-related macular degeneration using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A) 6 x 6 mm en-face images of the right eye. (A1) En-face structural OCT at the level of the RPE demonstrating GA. The area of GA is circumscribed in yellow, which is overlaid over the images in A2 and A3. (A2) En-face structural OCT at the level of the choriocapillaris demonstrating alteration in a similar area as the GA. (A3) OCT angiogram at the level of the choriocapillaris demonstrating flow impairment in a similar area as the GA. Larger choroidal vessels have been push inward into the area of choriocapillaris alteration so are seen in this 10micrometer slice. Detail is greatly improved over that of the en-face structural OCT. (A4) Corresponding OCT b-scan shows the loss of RPE causing increased intensity below Bruch’s membrane which is characteristic of GA. (B) 3 x 3 mm en-face images of the left eye. (B1) En-face structural OCT at the level of the RPE demonstrating GA. The area of GA is circumscribed in yellow, which is overlaid over the images in B2 and B3. (B2) En-face structural OCT at the level of the choriocapillaris demonstrating alteration in a similar area as the GA. (B3) OCT angiogram at the level of the choriocapillaris demonstrating flow impairment in a similar area as the GA. Larger choroidal vessels have been push inward into the area of choriocapillaris alteration so are seen in this 10micrometer slice. Detail is greatly improved over that of the en-face structural OCT. (B4) Corresponding OCT b-scan shows the loss of RPE causing increased intensity below Bruch’s membrane which is characteristic of GA.

Figure 7

OCTA and FA/ICGA of CNV in Neovascular AMD. The left eye of a 67 year old Caucasian man with choroidal neovascularization (CNV) due to neovascular age-related macular degeneration using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A) 6 x 6 mm OCT angiogram segmented so both the choriocapillaris and the outer retina are shown. A circular net of abnormal vessels are shown surrounded by relatively homogenous choriocapillaris. The abnormal vessels exist both below and above Bruch’s membrane (in the outer retina). (B) En-face structural OCT with a red line corresponding to the highly-sampled OCT b-scan in C. (C) 12 mm highly sampled OCT b-scan through the fovea demonstrates a large retinal pigment epithelial detachment, subretinal fluid, disruption of Bruch’s membrane, and hyper-reflective material characteristic of CNV. (D) Indocyanine green angiography early, intermediate, and late frames show increasing hyper-fluorescence and pooling of dye in the CNV. (E) Fluorescein angiography intermediate and late frames show increasing hyper-fluorescence and pooling of the CNV.

Figure 8

OCTA and FA of CNV in Neovascular AMD. (A) The right eye of a 63 year old Caucasian man with choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (AMD) using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) 3 x 3 mm OCT angiogram segmented so both the choriocapillaris and the outer retina are shown. Two nets of abnormal vessels are shown surrounded by relatively homogenous choriocapillaris. The abnormal vessels exist both below and above Bruch’s membrane (in the outer retina). (A2-3) En-face structural OCT with a red line corresponding to a 12 mm highly sampled OCT b-scan (cropped to 3 mm) through the macula. The OCT b-scan demonstrates a retinal pigment epithelial detachment (RPED), subretinal fluid, an intraretinal cyst, and hyper-reflective material characteristic of CNV. (A4-6) Fluorescein angiography (FA) early, intermediate, and late frames showing increasing hyper-fluorescence and staining of the CNV. (B) The left eye of an 89 year old Caucasian woman with CNV type three (retinal angiomatous proliferation, RAP) due to neovascular AMD using the Angiovue OCTA software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (B1) 6 x 6 mm OCT angiogram segmented at the outer retina showing a round RAP lesion (yellow arrow). A feeder vessel from a retinal vessel was noted (not shown). (B2) Color fundus photo demonstrating hemorrhage in the region of the RAP lesion. (B3) 6 mm highly sampled OCT b-scan through the macula shows subretinal and intraretinal fluid and a round ball of hyper-reflective tissue above a serous RPED. (B4-6) FA early, intermediate, and late frames showing increasing hyper-fluorescence and pooling in the CNV.

Figure 9

OCTA of CNV in Neovascular AMD. (A) The left eye of an 89 year old Caucasian man with choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (AMD) using the swept source optical coherence tomography angiography (OCTA) prototype (Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachussetts Insitute of Technology, Cambridge, MA). (A1) 3 x 3 mm OCT angiogram of the outer retina with manual removal of the retinal vessel ghost artifact. A sea-fan appearing CNV is seen. (A2) Corresponding OCT b-scan showing a retinal pigment epithelial detachment, disruption of Bruch’s membrane, and hyper-reflective material characteristic of CNV. (B) The left eye of a 70 year old Caucasian man with treatment-naïve choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (AMD) using the swept source OCTA prototype (Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachussetts Insitute of Technology, Cambridge, MA). (B1) 3 x 3 mm OCT angiogram of the outer retina with manual removal of the retinal vessel ghosting artifact. A sea-fan appearing CNV is seen. (B2) Red-free fundus photo exhibiting a lesion of the same shape and location as the CNV seen in B1.

Figure 10

OCTA and FA of Microaneurysms in NPDR. The right eye (A) and left eye (B) of a 45 year old Caucasian man with non-proliferative diabetic retinopathy using the swept source optical coherence tomography angiography (OCTA) prototype (Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachussetts Insitute of Technology, Cambridge, MA). (A1) Fluorescein angiography (FA) cropped to approximately 6 x 6 mm. Aneurysms are circled in yellow. (A2) Full-thickness (internal limiting membrane to Bruch’s membrane) 6 x 6 mm OCT angiogram. FAZ appears enlarged. Aneurysms that are seen on FA in A1 that are also seen on OCTA are circled in yellow. Aneurysms on FA that are seen as areas of capillary non-perfusion on OCTA are circled in blue. Areas where aneurysms are seen on FA, but show normal vasculature on OCTA are circled in red. (B1) FA cropped to approximately 3 x 3 mm. Aneurysms are circled in yellow. (B2) Full-thickness 3 x 3 mm OCT angiogram, which provides improved detail over 6 x 6 mm OCT angiograms, demonstrates higher sensitivity in detecting micro vascular abnormalities. FAZ appears enlarged. Aneurysms that are seen on FA in B1 that are also seen on OCTA are circled in yellow. Aneurysms on FA that are seen as areas of capillary non-perfusion on OCTA are circled in blue.

Figure 11

OCTA of NPDR. The right eye (A) and left eye (B) of a 58 year old Caucasian man with non-proliferative diabetic retinopathy and diabetic macular edema (DME) using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) Full-thickness (internal limiting membrane to Bruch’s membrane) 6 x 6 mm OCT angiogram shows microvascular abnormalities such as areas of capillary non-perfusion (yellow arrows), capillary loops, and microaneurysms. (A2) En-face structural OCT with a red line corresponding to the highly-sampled OCT b-scan in A3. (A3) 12 mm highly sampled OCT b-scan through the fovea demonstrating DME and hard exudates. (B1) Full-thickness 3 x 3 mm OCT angiogram, which provides improved detail over 6 x 6 mm OCT angiograms, shows microvascular abnormalities such as areas of capillary non-perfusion (yellow arrows), capillary loops, and microaneurysms. (B2) En-face structural OCT with a red line corresponding to the highly-sampled OCT b-scan in B3. (B3) 12 mm highly sampled OCT b-scan through the fovea demonstrating DME and hard exudates.

Figure 12

OCTA of Neovascularization in PDR. (A) The right eye of a 74 year old African woman with neovascularization of the disc (NVD) due to proliferative diabetic retinopathy (PDR) using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) Color fundus photo demonstrating fine neovascular vessels over the optic disc. (A2) Full-thickness (internal limiting membrane to Bruch’s membrane) 3 x 3 mm OCT angiogram at the optic disc. Wispy NVD is difficult to appreciate. (A3) 3 x 3 mm OCT angiogram at the optic disc segmented with the inner boundary in the vitreous above the NVD and the outer boundary slightly below the internal limiting membrane (ILM). The NVD is clearly appreciable. (A4) En-face structural OCT showing abnormal tissue at the optic disc. (A5) Highly-sampled OCT b-scan of the optic disc where abnormal tissue is observed extending above the ILM into the vitreous cavity. (B) The right eye of a 46 year old African woman with neovascularization elsewhere (NVE) due to proliferative diabetic retinopathy (PDR) using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (B1) 3 x 3 mm OCT angiogram with the inner boundary in the vitreous and the outer boundary at Bruch’s membrane. Abnormal vessels are seen in an area of capillary non-perfusion. Image quality is limited by artifact from movement (horizontal and vertical lines). (B2) Corresponding OCT b-scan showing abnormal tissue above the ILM extending into the vitreous cavity.

Figure 13

OCTA of BRAO and CRAO. (A) The right eye of a 70 year old Caucasian man with an acute branch retinal artery occlusion using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) Full-thickness (internal limiting membrane to Bruch’s membrane) 4.5 x 4.5 mm OCT angiogram of the optic disc showing decreased capillary perfusion superotemporal and nasal to the disc (yellow arrows). (A2) 4.5 x 4.5 mm en-face OCT thickness map showing retinal thickening in red and thinning in blue (yellow arrows) that correspond to the decreased capillary perfusion in A1. (A3) Full-thickness 6 x 6 mm OCT angiogram illustrating decreased capillary perfusion superotemporal and nasal to the disc (yellow arrow) as in A1. (A4) 6 x 6 mm en-face OCT thickness map showing retinal thickening in red (yellow arrow) that correspond to the decreased capillary perfusion in A3. (B) The right eye of an 81 year old Caucasian man with a subacute central retinal artery occlusion using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (B1) Full-thickness 4.5 x 4.5 mm OCT angiogram of the optic disc showing diffusely decreased peripapillary capillary perfusion. (B2) Full-thickness 6 x 6 mm OCT angiogram illustrating decreased capillary perfusion in the macula. Only the large retinal and peripapillary vessels demonstrate blood flow. (B3) Fluorescein angiography is hypo-fluorescent in the macula and peripapillary region due to the decreased ability for the fluorescein dye to reach these areas because of low blood flow. The vessels appear attenuated. (B4) Red-free fundus photo demonstrates attenuation of the vessels especially in the macular and peripapillary regions.

Figure 14

OCTA of BRVO and CRVO. (A) The left eye of a 61 year old Asian woman with a chronic branch retinal vein occlusion using the Angiovue optical coherence tomography angiography (OCTA) software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (A1) Full-thickness (internal limiting membrane to Bruch’s membrane) 3 x 3 mm OCT angiogram showing capillary non-perfusion superotemporal extending into the foveal avascular zone (FAZ) and telangiectatic vessels at the border of the ischemic areas. (A2) Full-thickness 6 x 6 mm OCT angiogram demonstrating that the capillary non-perfusion is along the superior arcade. The edges of the ischemia are bordered by telangiectatic vessels, capillary loops, and possible microaneurysms. (A3) En-face structural OCT with a retinal thickness map and a red line corresponding to the highly-sampled OCT b-scan in A4. (A4) 12 mm highly sampled OCT b-scan through the fovea which appears relatively unaffected. (A5) Retinal thickness map demonstrating superior thickening due to edema. (B) The left eye of a 72 year old Caucasian man with a chronic central retinal vein occlusion using the Angiovue OCTA software of the RTVue XR Avanti (Optovue, Inc., Fremont, CA). (B1) Full-thickness 3 x 3 mm OCT angiogram showing diffuse capillary non-perfusion continuous with the FAZ and telangiectatic vessels. (B2) Full-thickness 6 x 6 mm OCT angiogram demonstrating telangiectatic vessels and diffuse capillary non-perfusion especially along the inferior arcade. (B3) En-face structural OCT with a retinal thickness map and a red line corresponding to the highly-sampled OCT b-scan in B4. (B4) 12 mm highly sampled OCT b-scan through the fovea which shows macular edema and disruption of the photoreceptor layer. (B5) Retinal thickness map demonstrating thickening that is greatest inferiorly.