Article

Retinal Vascular Imaging With OCTA

High-resolution images of the retinal and choroidal vasculature.

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OCT angiography (OCTA) was first approved by the FDA in late 2015 for ophthalmic applications and has since garnered a great deal of attention. It uses the variable backscattering of light from vascular (mobile red blood cells) to reliably create high-resolution images of the retinal and choroidal vasculature. In addition, OCTA continues to provide the structural B scans to which we have grown accustomed with previous versions of OCT technology. Because of its ability to provide depth-resolved imaging of capillaries in a manner that has not previously been possible, OCTA has many potential clinical and research applications, including for retinal vascular diseases like diabetic retinopathy (DR) and macular telangiectasia (MacTel), as well as age-related macular degeneration (AMD) and ocular inflammatory disease.1,2

OCTA VS DYE-BASED ANGIOGRAPHY IN RETINAL VASCULAR DISEASE

Although OCTA technology is still in its infancy, it has already exhibited some distinct advantages over more traditional, invasive, dye-based tests. In addition to eliminating the need for dye, and thereby reducing injection-related complications,3,4 and eliminating the narrow “transit window” seen with both fluorescein angiography (FA) and indocyanine green angiography (ICG), OCTA does not suffer from the potential obscuration of retinal and vascular features that may occur with dye leakage.5 Additionally, multiple authors have demonstrated the ability of OCTA to resolve capillary-level detail with remarkable depth resolution,6-9 and detail approaching that of histologic studies.7-10

Several studies have suggested either the superiority or noninferiority of OCTA imaging when compared to FA for various types of macular disease. In ischemic vasculopathies like DR and retinal vein occlusion (RVO), OCTA can detect areas of hypo- and nonperfusion in all retinal layers with excellent accuracy and reliability. Similar studies have shown that FA cannot resolve the deep capillary plexus or peripapillary radial capillaries at all.8,11 A number of studies examining DR and RVO have shown that most, if not all, of the clinically relevant macular findings are demonstrable with OCTA.2,12,13 Considering the qualitative nature of FA when attempting to assess retinal capillary density,14 OCTA will likely prove to be the superior tool in quantitatively evaluating the severity of retinal ischemia, especially as the ability to image the retinal periphery improves. On a practical level, OCTA provides real-time information about the severity of ischemia in diabetic and vein occlusion subjects which can help physicians in assessing visual prognosis more readily.

While physicians still need to and should perform wide-field FA to assess for the presence of peripheral neovascularization and nonperfusion, OCTA can detect both neovascularization of the disc (NVD) and elsewhere (NVE) reliably, assuming the pathology is within the field-of-view.15-17 Areas in which the management of DR may change or even benefit are quantification and monitoring of retinal capillary perfusion while treating patients with anti-VEGF agents. It has been suggested that retinal hypo- or non-perfusion may be prevented, or even reversed with sustained anti-VEGF therapy,18 and OCTA provides a relatively easy and non-invasive method for assessing response to treatment in this regard. Further, OCTA may prove to be invaluable in the detection of subclinical disease, where FA is not currently useful or indicated.2,13,19

OCTA IN NEOVASCULAR AMD AND CHOROIDAL NEOVASCULARIZATION OF OTHER CAUSES

OCTA has also shown significant potential for assessing neovascular activity in the setting of neovascular (nvAMD), as well as choroidal neovascularization (CNV) of other causes (eg, myopia, vitelliform dystrophies).1,2,20,21 Differentiating vascular from avascular components of subretinal fibrosis and subretinal hypereflective material (SHRM) has proven difficult with structural OCT alone, and the staining patterns seen on FA and ICG are often not particularly helpful.

The ability of OCTA to confirm the presence of choroidal neovascular membranes is very useful, although doing so can be time-consuming and require significant manual segmentation on the part of the practitioner (Figures 1 and 2). However, in at least some cases, the high reflectivity of the retinal pigment epithelium (RPE) attenuates the sub-RPE signal to a degree that reliable imaging of Type 1 CNV is not possible or reliable, at least with spectral domain OCTA.

Figure 1. Fluorescein angiography, ICG, and OCTA (Zeiss Angioplex) of a patient with a known history of dry AMD. Early FA without evidence of pathology or vascular abnormalities (A). Late staining / leakage seen in the superior macula concerning for possible CNV (B). Depth-encoded retinal OCTA (6 mm x 6 mm) demonstrates no obvious retinal vascular abnormalities (C). Early ICG demonstrates patchy choroidal filling (D), while late ICG (E) demonstrates macular flow voids without any hyperfluorescence or vascular leakage. En-face OCTA through the outer retina (segmentation demonstrated in image G) shows no evidence of CNV/vascular structures in area corresponding to area of late hyperfluorescence seen on FA (F, G). In this case, the lack of nonspecific background staining allows OCTA to clearly demonstrate the lack of CNV, whereas FA is ambiguous. Use of OCTA in this case may obviate the need for further invasive dye testing to monitor this patient.

Figure 2. Fluorescein angiography, ICG, and OCTA (Zeiss Angioplex) in an individual with a known history of dry AMD. Both early (A) and late (B) FA show varying degrees of hyperfluorescence, raising some concern for development of a neovascular membrane. Depth-encoded OCTA of the retinal vasculature (6 mm x 6 mm) without obvious abnormal vascular structures (C). Both early and late ICG show mild hyperfluorescence and perhaps some mild leakage corresponding to area of hyperfluorescence seen on FA (D, E). En-face OCTA of the choriocapillaris and outer retina (due to irregular automated segmentation) shows a neovascular membrane present within the pigment epithelial detachment (PED) seen within the B-scan (G) (green areas denote flow within the PED).

While the presence of choroidal neovascularization in the absence of symptoms, hemorrhage, or active exudation has previously gone undetected, the ability to diagnose these subclinical lesions may alter the course of the associated disease processes, and potentially allow treatment of these neovascular processes before catastrophic hemorrhage occurs. The clinical significance of asymptomatic choroidal neovascularization is currently being investigated.

OCTA IN UVEITIS AND OCULAR INFLAMMATORY CONDITIONS

Many imaging modalities are still essential to diagnosis and monitoring treatment response in ocular inflammatory syndromes. In the various “white dot” syndromes and chorioretinitis, characteristic findings on FA and ICG are often very helpful in clinching a diagnosis, and fundus autofluorescence has become increasingly popular to assess for disease activity while patients undergo treatment. Assessment of macular involvement in uveitis has been largely limited to the measurement of retinal thickness with OCT,22 but multiple authors recently have begun to explore the potential for OCTA to further understand retinal vascular changes in uveitis.23-25 For example, Kim et al demonstrated that subjects with chronic uveitis have subclinical capillary loss in the macula on OCTA that was not clinically detected.23 Levison et al have published data describing the macular vascular changes and complications in patients with uveitis using OCTA,26 which appears to superior to FA in at least some cases.

Disease entities in which OCTA could potentially be beneficial, in the authors’ opinion, are retinal vasculitis, and intermediate uveitis. As is evident in noninflammatory retinal vascular diseases, OCTA appears superb in assessing retinal perfusion quantitatively and objectively. In conditions like Behcet’s disease and lupus-associated retinal vasculitis, objective measurements of retinal perfusion could serve as indicators of disease activity and response to treatment (Figure 3). Further, as widefield capabilities improve, assessment of larger areas of retinal vasculature and more peripheral retina may be helpful in conditions like Eales disease, and in evaluating the peripheral retinal nonperfusion that can occur in intermediate uveitis.27

Figure 3. Widefield FA and OCTA (6 mm x 6 mm) (Zeiss Angioplex) in a young woman with a diagnosis of lupus-associated retinal vasculitis. Widefield FA of the right (A) and left (B) eyes demonstrates marked retinal nonperfusion, as well as some areas of vascular leakage and/or staining. Depth-encoded OCTA of both retinas clearly shows the extent of macular ischemia in both eyes but also demonstrates the limited field-of-view in comparison to widefield FA (C, D).

CONCLUSIONS

Despite the promise OCTA shows in changing our understanding of, as well as ability to diagnose and monitor treatment of, various types of ophthalmic disease, the technology carries with it some limitations. The need for manual segmentation of retinal layers to extract valuable information from the acquired images can be time consuming. This should improve significantly as automated segmentation becomes more robust. At the moment, commercially available OCTA platforms allow imaging of 3 mm x 3 mm, 6 mm x 6 mm, and 8 mm x 8 mm. However, certain platforms currently available only for research purposes, like the swept-source-based Zeiss Plex Elite 9000, offer wider-angle montage capabilities (Figure 4), which could prove interesting in quantitative perfusion analyses and the evaluation of peripheral retina.

Figure 4. Both A and B represent widefield montages in a normal patient reconstructed by the currently research-only swept-source-based Zeiss Plex Elite 9000 OCTA platform, and demonstrate the potential wide-angle imaging capabilities of OCTA.

Just as the adoption of OCT was initially slow, we’re likely just beginning to understand the value of OCTA in the management of patients with retinal disease and ocular inflammatory diseases. Improvements in imaging speed, layer segmentation, and wide-field capabilities will present powerful and effective methods for examining the retinal vasculature and likely shed light on the pathophysiology of various types of disease that manifest within the posterior segment. RP

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