Treating sight-threatening retinopathy using OCTA

In 2015, the FDA approved the first optical coherence tomography angiography (OCTA) in the United States. Since then, many optical coherence tomography (OCT) manufacturers have integrated angiography technology into their devices. This technology allows for non-invasive visualization of retinal and choroidal blood vessels and enhances patient management. This article will review the optical concepts of OCTA, including benefits of standard fluorescein angiography (FA), and provide a comprehensive discussion of 2 common retinal conditions in which OCTA is extremely useful in clinical practice: age-related macular degeneration (AMD) and diabetic retinopathy (DR).

Basics of OCTA

OCT uses light rays to construct cross-sectional views of the retina.¹ The retinal layers are differentiated because of their reflective properties. Simply, OCTA uses light rays to detect change in OCT images over a short period. The variation identified corresponds to red blood cell movement within normal or abnormal vascular networks.¹ This noninvasive imaging technique allows for visualization of many types of vascular pathology including retinal and choroidal neovascularization, macular telangiectasia, retinal ischemia, and retinal macro/ microaneurysms (MAs).¹

Standard OCT analysis has been able to provide eye care practitioners with qualitative and quantitative analysis of the retina, the optic nerve, and the anterior segment. Qualitative images provide detailed anatomical views. When practitioners are evaluating patients for retinal disease, these scans are helpful for detecting anatomical variations such as intraretinal and subretinal edema, changes to the vitreoretinal interface, and outer retinal atrophy. Quantitative analysis of the retina provides retinal thickness measurements. Retinal thickness variations can be useful for detecting disease and monitoring progression and/or response to therapy.

OCTA provides qualitative images that allow for visualization of vasculature. With OCTA, practitioners do not acquire temporal images as they do with typical FA; instead, 1 vascular image is acquired. The image can be segmented into en face layers (vitreoretinal interface, superficial retina, deep retina, avascular, choriocapillaris, and choroid) to enhance vascular analysis (Figure 1). A color-coded depth map of the en face images is created to provide an overview of the vascular network.¹ As with other imaging techniques, practitioners must understand normal OCTA images to ensure that subtle abnormalities are found when pathology is present.

In 2018, the FDA approved the first quantitative analysis for one of the commercially OCTA devices (AngioVue; Optovue). Instead of providing a thickness measurement as standard retinal OCT does, OCTA quantitative analysis provides measurements of vascular density and the total area of the foveal avascular zone. These measurements can be helpful for identifying and monitoring retinal ischemia.

The good and the bad of OCTA

Using OCTA has several benefits. As mentioned, obtaining OCTA images is non-invasive. Acquisition of 1 image typically takes 3 to 6 seconds, and unlike standard FA, it is performed without an injected dye. This quick acquisition and the reduced risk of anaphylactic allergy are 2 benefits of using the technology. Another benefit over FA is the ability to segmentally visualize vascularization (Figure 1).¹

Understanding OCTA’s downfalls can aid in interpretation and allow providers to determine when a standard FA is warranted. Scan quality can be altered because of media opacifications, eye movements creating motion artifacts, or segmentation errors. OCTA is unable to image low-flow areas, although newer OCT devices using swept-source technology may offer enhanced capability of imaging these areas. OCTA also cannot detect leakage from vessels because of slow leakage rate—this can make differentiating between retinal neovascularization and intraretinal microvascular abnormalities difficult.¹ Lastly, OCTA imaging cannot determine vascular filling times, which is helpful when evaluating patients for vascular occlusions.

OCTA in clinical practice

Systematic analysis of OCTA starts with a generalized overview of the color-coded map to help identify areas of abnormalities (Figure 2). Next, retinal segmentation should be analyzed to ensure that the en face vascular images are accurate (Figure 3). Lastly, the decorrelation signal on the OCT tomogram should be reviewed to understand where red blood cell movement was detected (Figures 2 and 3).

Importantly, practitioners must also to plan scans to ensure that regions in question are imaged. For example, imaging both the optic nerve and the macula in patients with diabetes is useful for detection on disc and retinal neovascularization.

AMD

AMD is one of the leading causes of irreversible vision loss in developed countries.² OCT and OCTA can be useful for early detection of progression from dry AMD to wet AMD.

Dry AMD

Dry AMD is the early stage of AMD and indicates the absence of a choroidal neovascular membrane. Dry macular degeneration changes include drusen and geographic atrophy.^1,2 Although retinal drusen are not accompanied by vascular changes on OCTA, their appearance on an OCTA image is worth discussing and noting.

Drusen are pigment epithelial detachments filled with lipid debris from the photoreceptors. OCT B-scans (Figure 4) will show drusen as a dome-shaped elevation in the retinal pigment epithelium (RPE) with sub-RPE hyper-reflectance.² En face OCTA images will demonstrate hyperreflective lesions in the deep and/or avascular regions depending on the size of the drusen because of improper segmentation (Figure 5).²

Geographic atrophy (GA) is a sign of advanced macular degeneration; the clinical picture is atrophy of the photoreceptors, RPE, and choriocapillaris, which can be visualized on OCT B-scan images (Figure 6). With the loss of the highly pigmented RPE, light rays penetrate deeper, enhancing subretinal illumination in areas of GA. OCTA imaging of GA will show an attenuation of the choriocapillaris within and surrounding areas of GA.² OCTA scans will also provide improved visualization and a false appearance of increased red blood cell flow within these choroidal vessels because of improved subretinal illumination (Figure 7). It is important to differentiate normal choroidal anatomy from that of a choroidal neovascular membrane.

Wet AMD

Wet macular degeneration, another type of advanced AMD, is responsible for a majority of vision loss from the disease.^1-3 The term wet indicates the development of a choroidal neovascularization membrane (CNVM). In AMD, 3 types of neovascularization can be seen, but 2 types are more prevalent. Occult CNVM (type 1) comprises membranes that lie underneath the RPE. Classic CNVM (type 2) involves neovascular membranes found above and below the RPE.

Subretinal fluid, intraretinal fluid, and pigment epithelial detachments on standard OCT B-scans are good indicators of the presence of CNVM (Figure 8). OCTA has been shown to be approximately 70% effective at detecting CNVM.³ Both classic and occult CNVM can be visualized; however, classic membranes are identified with more success.³ Because of this, standard fluorescein angiography is still useful in cases of wet AMD.

Different patterns of CNVM have been identified on OCTA, with a sea fan appearance being the most common type (Figure 9). Other configurations commonly identified are nodular (Figure 10) and circular (Figure 9). Use of OCT B-scan images in conjunction with OCTA images, early detection, and monitoring of treatment response can be accomplished (Figure 10 and Figure 11).

Diabetic retinopathy

DR is the leading cause of vision loss worldwide. OCTA is able to detect changes in nonproliferative DR (NPDR) and proliferative DR (PDR).¹

NPDR

OCTAcan detect many changes associated with this condition, including microaneurysms (MAs), retinal ischemia, and intraretinal microvascular abnormalities.¹ OCT analyses of the superficial and deep retina are helpful for detecting these changes.

MAs appear as saccular dilations of the capillaries. They can be easily identified in the superficial and deep retinal layers (Figure 12). Identification of MAs using OCTA is superior to a standard clinical exam; however, if an FA and an OCTA of the same eye were compared, the FA image would show more MAs than the OCTA image because of the low blood flow through the MAs.¹

Retinal ischemia or capillary dropout can be easily visualized using OCTA. Ischemia can be foveal or non-foveal (Figure 12). Foveal ischemia, also called macular ischemia, is an increased size of the foveal avascular zone. This change can be accompanied by changes to best corrected acuity. A higher amount of retinal ischemia is correlated with risk of development of proliferative retinopathy.¹ Both the deep and superficial layers will allow for visualization of the capillary dropout. Areas of retinal ischemia will also be represented on standard OCT B-scan images as a reduction in retinal thickness (Figure 13). Intraretinal MAs on OCTA appear as dilated terminal blood vessels in areas of retinal ischemia (Figure 12). OCTA is more sensitive at detecting intraretinal MA than a typical clinical exam is.^1,4

PDR

PDR indicates the development of neovascularization secondary to retinal ischemia. The neovascularization in diabetes is classified as neovascularization of the disc and includes a 1 disc diameter (DD) area around the optic nerve head or neovascularization elsewhere (NVE), which is retinal neovascularization that is greater than 1 DD away from the optic nerve head. OCTA images should be acquired overlying the optic nerve, in the macula, and over any areas that are suspicious of NVE on clinical examination. Retinal neovascularization has 3 distinct forms⁵:

– Type 1: Originating from retinal venules, tree-like appearance on OCTA extending into the vitreous (Figure 14)

– Type 2: Originating from the capillary plexus, located in the inner nuclear layer

– Type 3: Originating from intraretinal MAs, sea fan appearance on OCTA (Figure 15)

Anterior segment OCTA technology is not yet clinically available. Such technology has shown the ability to detect angle and iris neovascularization, which will be helpful for a more detailed analysis of the anterior segment in patients with PDR.⁶

References

1. Kashani AH, Chen C, Gahm JK, et al. Optical coherence tomography angiography: a comprehensive review of current methods and clinical applications. Prog Retin Eye Res. 2017;60:66-100. doi:10.1016/j.preteyeres.2017.07.002

2. Roisman L, Goldhardt R. OCT angiography: an upcoming non-invasive tool for diagnosis of age-related macular degeneration. Curr Ophthalmol Rep. 2017;(5)2:136-140. doi:10.1007/s40135- 017-0131-6

3. Malamos P, Tsolkas G, Kanakis M, et al. OCT-angiography for monitoring and managing neovascular age-related macular degeneration. Curr Eye Res. 2017;42(12):1689-1697. doi:10.108 0/02713683.2017.1356336

4. Simouchi A, Ishibazawa A, Ishiko S, et al. A proposed classification of intraretinal microvascular abnormalities in diabetic retinopathy following panretinal photocoagulation. Invest Ophthalmol Vis Sci. 2020;61(3):34. doi:10.1167/iovs.61.3.34

5. Ishibazawa A, Nagaoka T, Yokota H, et al. Characteristics of retinal neovascularization in proliferative diabetic retinopathy imaged by optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57(14):6247-6255. doi:10.1167/ iovs.16-20210

6. Lee WD, Devarajan K, Chua J, et al. Optical coherence tomography angiography for the anterior segment. Eye Vis (Lond). 2019;6:4. doi:10.1186/s40662-019-0129-2