Why Use Optical Coherence Tomography Angiography for Disc Assessment in Glaucoma?

Vascular dysregulation of the optic nerve head and the peripapillary retina is considered as one of the risk factors for the development and progression of open-angle glaucoma.¹ In addition, glaucomatous neuroretinal rim and retinal nerve fiber layer loss is associated with reduced perfusion of the optic nerve head and peripapillary retina in all types of glaucoma. Therefore, in recent decades, various techniques have been used for noninvasive measurement of disc and peripapillary perfusion.^2,​3,​4 However, vascular structures and their regulation in the disc and the peripapillary retina differ both across the retinal layers and between the retina and choroid, respectively. Noninvasive clinical techniques available in the past decades could not optimally separate perfusion-related information arriving from the different layers.^2,​3 This is why research focused on global measures of ocular perfusion, such as retrobulbar perfusion, global retinal oxygenation, and ocular perfusion pressure.⁴

In contrast to the earlier technologies, precise segmentation in modern optical coherence tomography (OCT) makes it possible to accurately separate both the retinal layers (structural information) and the perfusion maps of the individual layers (functional information).^{5,​6,​7,​8,​9} This enables clinicians to evaluate the corresponding structural and functional information (en face angiograms and en face retinal images), layer by layer, in a noninvasive manner. In practical terms, if a clinician detects an abnormality suggestive for glaucomatous damage, he or she can analyze the layers separately and can focus only on the corresponding structural and functional properties of the layer of interest. The perfusion-related functional data and the structure-related anatomical data provide complementary information.

In addition to qualitative evaluation, precise measurement of perfusion is also important when decreased vascularity or perfusion is investigated in glaucoma. OCT angiography offers options for both qualitative evaluation and quantitative measurement of disc and peripapillary perfusion. The quantitative parameters are vessel density (expressed in % of vessels in the measured area within a well-defined retinal layer) and flow index (the mean decorrelation value of the whole en face angiogram).^{5,​6,​7,​8,​9} These parameters have been shown to be reproducible both in normal and in glaucomatous eyes; decreased in glaucoma; and their reduction is related to glaucomatous visual field deterioration, retinal nerve fiber layer thickness, inner macular retina thickness, and the stage of glaucoma.^{5,​6,​7,​8,​9}

It is important to note that advanced glaucomatous disc and retinal nerve fiber layer damage builds up from localized defects; thus, in many early and moderately severe glaucoma cases, only localized neuroretinal rim and retinal nerve fiber layer defects are present. The most typical locations of these localized defects are the inferotemporal and superotemporal disc and peripapillary sectors. When a glaucomatous eye with a localized damage is investigated, it is more informative to measure perfusion in the damaged area separately than to use perfusion data of the whole disc or peripapillary area, because signals arriving from the normal areas diminish the impact of the locally reduced perfusion on the result. In order to offer separate sector analysis for peripapillary vessel density measurement, the AngioVue OCT (AngioVue/RTVue-XR Avanti OCT, Optovue Inc., Fremont, CA) employs a recently introduced software version (the Optovue 2015.100.0.33 software version). In this chapter, clinical cases imaged using that instrument and software version are presented. Recently, it has been shown that sector vessel density measured in the retinal nerve fiber layer may decrease prior to the development of clinically significant retinal nerve fiber layer thinning and visual field deterioration, and that it spatially corresponds to the thinned retinal nerve fiber bundles.⁸ It is important to emphasize that OCT angiography is based on the detection of moving red blood cells; thus, nonperfused vessels (during strong vasoconstriction), vessels filled with static blood (vessel occlusion), and extravasal blood (bleeding) are not recognized by this technology.

16.2 Determination of Disc and Peripapillary Vessel Density with Optical Coherence Tomography Angiography

The AngioVue OCT obtains amplitude decorrelation angiography images.^{5,​6,​7,​8,​9} This means that only the moving elements (the circulating red blood cells) provide perfusion-related information. The A-scan rate is 70,000 scans per second, the light source is centered on 840 nm, and a bandwidth of 50 nm is used. Each OCT angiography volume contains 304 × 304 A-scans with two consecutive B-scans captured at each fixed position before proceeding to the next sampling location. Split-spectrum amplitude-decorrelation angiography is used to extract the OCT angiography information. Motion correction to minimize motion artifacts arising from microsaccades and fixation changes is used. OCT angiography information is displayed as the average of the decorrelation values when viewed perpendicularly through the thickness. Six peripapillary sectors ( ▶ Fig. 16.1) and four en face imaging retinal layers are automatically given by the software. The software-provided peripapillary sectors are based on the Garway-Heath map.¹⁰ The corresponding en face vessel density and retinal layers from the vitreous to the choroid are (1) the optic nerve head layer (the innermost layer), (2) the vitreous–retina border, (3) the layer of the radial peripapillary capillaries on the OCT angiography image paired with the retinal nerve fiber layer on the structural retinal image, and (4) the retina–choroid border. Using the “angio structure-function” overview presentation, the subsequent OCT angiography images are shown in the above order in the upper horizontal row, and the corresponding structural images in the lower horizontal row. In OCT angiography for glaucoma assessment, the radial peripapillary capillaries layer is the most important one, since it represents perfusion in the retinal nerve fiber layer. The radial peripapillary capillaries layer is defined as all tissues between the outer limit of the retinal nerve fiber layer and the internal limiting membrane. The other layer that is relevant for the differential diagnosis in glaucoma is the optic nerve head layer spreading from the internal limiting membrane toward the vitreous body in a 150-µm thickness. Usually the 4.5 × 4.5 mm² scan size is used for glaucoma investigations. The inner elliptical contour (which defines the optic nerve head) is obtained by automatically fitting an ellipse to the disc margin based on the OCT en face image. The peripapillary area is defined as the area between the inner and outer ellipses. The ring width between the inner and outer elliptical contour lines is usually 0.75 mm. No pupil dilation is needed for optimal image quality (Signal Strength Index >50).

16.3 Optical Coherence Tomography Angiography of the Healthy Disc

▶ Fig. 16.1 shows disc and peripapillary vessel density measured with OCT angiography in the radial peripapillary capillaries layer, and the corresponding inner macula retinal thickness (ganglion cell complex [GCC]) map, 360-degree retinal nerve fiber layer thickness map, and symmetry graph of the healthy right eye of a 64-year-old female subject. The peripapillary vessel density measurement area ( ▶ Fig. 16.1a) is subdivided into six sectors: the superotemporal (ST), temporal (T), inferotemporal (IT), inferonasal (IN), nasal (N), and superonasal (NS) sectors. The corresponding en face structural image ( ▶ Fig. 16.1b) shows homogeneous normal reflectivity of the retinal nerve fibers in all sectors and in the total image area. Vessel density is 48.5% for the disc area, 59% for the total peripapillary area, and the sector vessel density values range between 55% (nasal) and 65.5% (temporal; ▶ Fig. 16.1c). This range is typical for healthy eyes in the radial peripapillary capillaries layer. Vessels (both the main retinal vessels and the capillary areas) are indicated with yellow and red on the color-coded vessel density map ( ▶ Fig. 16.1d). The intensity corresponds to the measured signal intensity. In OCT angiography, nonperfusion or poor perfusion is color coded with blue (not present on this image). The GCC map ( ▶ Fig. 16.1e) and the retinal nerve fiber layer thickness map ( ▶ Fig. 16.1f) are normal and within normal limits, and the retinal nerve fiber layer thickness symmetry is also within the normal limits ( ▶ Fig. 16.1g).

16.4 Comparison of Vessel Density between Healthy and End-Stage Glaucomatous Eyes

▶ Fig. 16.2 introduces into OCT angiography findings in glaucoma via the comparison of the vessel density map ( ▶ Fig. 16.2a), en face structural image ( ▶ Fig. 16.2b), and color-coded vessel density map ( ▶ Fig. 16.2c) of the end-stage glaucomatous right eye (cup/disc ratio 1.0) and the corresponding images and maps ( ▶ Fig. 16.2d, f) of the almost healthy, successfully trabeculectomized ocular hypertensive left eye of the same 48-year-old male patient. On the right eye, diffuse lack of vessels (lack of perfusion) is seen on the density map ( ▶ Fig. 16.2a). The darkness of the retinal nerve fiber layer (decreased light reflectivity due to diffuse retinal nerve fiber loss; ▶ Fig. 16.2b) is contrasted to the bright retinal nerve fiber layer of the left eye ( ▶ Fig. 16.2e). The color of the color-coded vessel density map of the right eye is bluish, while it is bright yellow and red for the left eye ( ▶ Fig. 16.2c,f). The GCC and retinal nerve fiber layer thickness values are outside the normal limits on the right eye and within the normal limits on the left eye ( ▶ Fig. 16.2g). The peripapillary sector vessel density values range from 40.8 to 47.5% on the right and from 53 to 59% on the left eye in the radial peripapillary capillaries layer.

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