32

Optical Coherence Tomography Angiography in Primary Open-Angle Glaucoma

David Huang, MD, PhD; Liang Liu, MD; and Michel Puech, MD, MSC

Primary open-angle glaucoma is a progressive optic neuropathy with the degeneration of the retinal ganglion cell bodies and axons, which results in cupping of the optic disc and characteristic patterns of visual field (VF) defects. VF testing remains essential for glaucoma assessment, but it has substantial variability, with poor reproducibility in some patients.^1,2 Structural studies^3–10 of the retinal nerve fiber layer (NFL) by optical coherence tomography (OCT) show its promise as an objective quantifiable measure for glaucoma assessment, but it has limited sensitivity for detecting early glaucoma, and only moderate correlation with VF loss. There is a growing body of evidence suggesting that glaucoma pathogenesis is associated with reduced blood flow in the optic nerve head (ONH) and retina.^11–13 Optical coherence tomography angiography (OCTA) has been shown to reliably detect glaucomatous changes in retinal and optic nerve circulation. The measurement of ONH blood flow and peripapillary retinal perfusion using OCTA has been found to be repeatable, reproducible, and detect glaucoma with high sensitivity.^11,14,15 This chapter reviews the results of early glaucoma studies using a custom swept source (SS)-OCT system, as well as the commercially available AngioVue OCTA system (Optovue Inc), which uses a high-speed (70 kHz) 840 nm spectral domain (SD)-OCT. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute the OCTA flow signal on both systems.^11,14,16

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF OPTIC DISC PERFUSION IN GLAUCOMA

Optic disc OCTA is a tool to study the role of ONH vascular insufficiency in the pathogenesis of glaucoma.^14,17 The ONH tissue is supplied by 2 main sources of blood flow: the prelaminar neural tissue is supplied by the central retinal artery, and the deeper layers (the lamina cribrosa and retrolaminar regions) by the posterior ciliary artery circulation.¹⁷ Previous reports indicate that the primary site of ONH damage in glaucoma is mainly nourished by the microcirculation of posterior ciliary artery.^12,17 Thus, it is useful to use OCTA to examine both the superficial and deep ONH circulation.

SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE OPTIC DISC

Jia et al¹¹ first quantified optic disc perfusion using SSADA on a custom SS-OCT system. The SS-OCT uses a longer central wavelength (1050 nm) than typical commercial retinal OCT systems (840 nm), and therefore can penetrate deeper into the ONH. Furthermore, SS-OCT is less susceptible to loss of OCT signal through the interferometric fringe washout phenomenon,18 and therefore can better image flow in the large retinal vessels in the ONH.

The 3-dimensional OCT angiogram was examined en face layer by layer (Figure 32-1). In examining these layered projections, one needs to keep in mind that large retinal vessels cast shadows on the tissue below. At the same time, flow from superficial vessels can also be projected onto highly reflective tissue below, which creates flow projection artifacts on structures such as the lamina cribrosa. Despite these artifacts, distinct patterns could be discerned in 3 planes. In the retinal plane (see Figure 32-1), the superficial disc vasculature blended seamlessly into the retinal vascular network. The retinal and superficial disc vascular networks were dense in the normal eye, but attenuated in the glaucomatous eye. In the choroid plane (see Figure 32-1), the angiogram is dominated by the near confluent peripapillary choriocapillaris. The disc circulation was sparse in this plane, which corresponds to roughly the deeper prelaminar tissue. In the scleral plane (see Figure 32-1), one would expect to see few vessels. The projection artifact, however, reproduces the dense choroidal flow pattern on the reflective scleral slab. Inside the disc, this slab corresponds roughly to the level of the lamina cribrosa, which had a dense vascular network in the normal eye clearly seen between the shadows of the large retinal vessels. The laminar vessels are attenuated in the glaucomatous eye. Overall, the impression was that glaucoma attenuated flow both in the microvascular network of both the superficial disc and the deeper lamina cribrosa.

To quantify the disc perfusion, the disc flow indices were computed by averaging decorrelation values within the disc margin in the en face whole-depth OCT angiograms. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% (coefficient of variation), respectively. The disc flow index in the glaucoma group was 25% lower (P = 0.003) compared with the normal group. In the glaucoma group, the disc flow index was significantly correlated with VF pattern standard deviation (PSD) and rim area (Figure 32-2). These correlations were significant even after accounting for age, cup/disc area ratio, NFL, and rim area. There was no overlap in flow index between the glaucoma and normal groups, but there was much overlapping between the 2 groups for the confocal scanning laser ophthalmoscopy rim area, cup/disc area ratio, and NFL thickness.¹¹

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE OPTIC DISC

The ONH circulation can also be imaged and measured using the commercially available AngioVue OCTA system using the “angio disc” scan. The disc boundary is automatically delineated by the AngioVue analytics software, and could be manually corrected using the OCT reflectance images (Figure 32-3). The whole-depth angiogram of the 4.5 × 4.5 mm optic disc area demonstrates a dense microcirculation in a normal disc (see Figure 32-3). AngioAnalytics software measures the vessel density inside the disc. Vessel density was automatically calculated as the proportion of analytic area occupied by blood vessels being defined as pixels having decorrelation values acquired by the SSADA algorithm above the threshold level. In this normal disc, the vessel density inside the disc was normal (65%; see Figure 32-3). Attenuation of the microvasculature network and focal capillaries dropout in a glaucomatous disc could be detected in a whole-depth en face OCTA (Figure 32-4). The vessel density inside the disc was abnormally low (53%; see Figure 32-4) in the glaucomatous eye.

Because the AngioVue is based on an SD-OCT system, it is more susceptible to the interferometric fringe washout artifact, in which OCT signal is lost in high-flow regions.¹⁸ There are absences of OCT signal in segments of blood vessels inside the normal disc (Figure 32-5). That makes the vessel density calculation less reliable in these cases. The loss of signal in rapidly moving fluids (known as flow voids) occurs because of washout of interferometric fringes within the OCT signal integration time. Fringe washout occurs at a lower velocity range in SD-OCT compared with SS-OCT, and would thus interfere with accurate measurement of ONH perfusion in spectral OCT. Fringe washout is not noticeable in disc vessels in both OCTA and structural OCT obtained by SS-OCT.

Using AngioVue OCTA, Wang et al¹⁹ found the flow index and vessel density of the optic disc were significantly correlated with VF mean deviation, NFL, and ganglion cell complex (GCC) thickness (all P < 0.01). The areas under the receiver operating characteristic (AROC) analysis also revealed that disc flow index and vessel density had the power to differentiate normal eyes from eyes with Primary open-angle glaucoma (AROC 0.82 and 0.80, respectively).

Chen et al²⁰ investigated the optic disc perfusion differences in glaucomatous and normal eyes using Cirrus 5000 HD-OCT-based (Carl Zeiss Meditec Inc) optical microangiography. Optical microangiography en face images for pre-lamina layer, lamina cribrosa, and the entire ONH (from the internal limiting membrane to the outer boundary of the choroid) were generated using maximum projection. Optic disc perfusion was measured by calculating the mean flow intensity within the optic disc. Optic disc perfusion was significantly lower in glaucomatous eyes compared to normal eyes in the pre-lamina layer (P = 0.024) and the entire ONH (P = 0.022), but not in the lamina cribrosa (P = 0.79).

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE PERIPAPILLARY RETINA IN GLAUCOMA

Because glaucoma primarily affects retinal ganglion cells and their axons, previous OCT studies used peripapillary NFL thickness measurements to detect glaucoma and its progression given its high reproducibility and diagnostic ability to distinguish normal and diseased eyes. A recent study showed the measurement of peripapillary retinal perfusion had a similar diagnostic performance compared with NFL thickness, but a better correlation with visual function. Using the commercially available AngioVue OCTA, the peripapillary microvasculature could be visualized with excellent capillary detail. The peripapillary retina also offers a larger area over which focal perfusion defects can be seen more easily. The tight correlation between blood flow measurements and VF in glaucoma may be useful to find the dysfunction in the neural structures, and that measurements of blood circulation can detect loss of function of nerve fibers or ganglion cells before thinning occurs. This would have potential for earlier diagnosis of glaucoma. On the OCT measurements of the NFL, the “floor effect” limits the ability to detect progression in advanced glaucoma eyes with severe NFL thinning. NFL thinning levels off at approximately 40 μm to 50 μm, perhaps because of residual glial tissue, blood vessels, or other non-neural tissue. The measurement of peripapillary retinal perfusion could overcome that problem and have potential for improving glaucoma monitoring.

Stay updated, free articles. Join our Telegram channel

Join