The Retinal Vessels
OCTA has significantly expanded our knowledge on the organization of the retinal vessels. The retinal vascularization may be separated into the following plexuses: the SCP, the MCP, the DCP, and the RPCP [
27‐
30]. The RPCP is unique in that it is mainly located within the superficial nerve fiber layer surrounding the optic disc.
Since the introduction of OCTA, a number of models have been proposed regarding connections among the retinal vascular plexuses [
29‐
32].
The SCP is a dense meshwork of vessels accommodated in the retinal ganglion cell layer (GCL) [
18]. The small capillaries arise from SCP arterioles and drain into SCP venules. The GCL slab enhances visualization of the capillary-free zones around the arteries and arterioles and helps differentiate arterial and venous systems [
32]. Using OCTA, SCP arterioles were demonstrated to be located more superficially than SCP venules [
30]. The SCP capillaries were shown to be arranged in a centripetal pattern in the macula and to converge on the parafoveal capillary ring [
29]. In the periphery, the superior and inferior circulations converge in an interlaced comb pattern [
29].
The SCP capillaries are connected with the other two layers of vessels at the inner plexiform layer/inner nuclear layer (IPL/INL) border (MCP) and inner nuclear layer/outer plexiform layer (INL/OPL) border (DCP). While the MCP colocalizes with the bipolar cell processes and amacrine cells, the DCP colocalizes with horizontal cells. These two plexuses are thus close to the high-oxygen-demand synapses of the IPL and OPL, respectively. The capillaries of the MCP and DCP have a lobular configuration without directional preference within their laminar planes [
29]. Because the MCP and DCP consist of capillaries of uniform size and are separated by only a small distance, they are often grouped together as the deep vascular complex (DVC).
Around the foveal avascular zone (FAZ), these three retinal capillary plexuses converge to form a single parafoveal capillary loop and collectively define the borders of the FAZ [
29]. Although some OCTA studies have separately investigated the FAZ area in different retinal capillary plexuses, recent papers have opted to assess this measurement in a single segment (whole retinal thickness). This choice was due to histologic and technical reasons: (1) there is a strong body of evidence suggesting the retinal plexuses merge at the edge of the FAZ, which may be thus considered a singular structure throughout the entire foveal thickness [
33]; and (2) assessing the FAZ size at different segments may lead to increased variability of measurements [
34]. The FAZ size was demonstrated to increase with age [
35,
36] and disease (e.g. myopia, hypertension) [
37,
38].
Recently, using higher-axial-resolution OCTA technology, Nesper and Fawzi [
30] identified distinct vascular connections from large-caliber arterioles and venules in the SCP to each of the three retinal capillary plexuses in healthy subjects. This organization accounts for the high oxygen demand of the plexiform layers that need highly oxygenated (arteriolar) blood in the MCP and DCP. Furthermore, they provided further evidence for the presence of vortices in the DCP, these draining into conduits which are straightly connected to venules in the SCP. Interestingly, collateral vessels crossing the horizontal raphe were identified at the DCP level. These crossing vessels were speculated to represent an alternative pathway of least resistance in the event of occlusive diseases. Nesper and Fawzi’s observations would appear to support the theory that each of the three plexuses has its own arteriolar supply and venular drainage, which would theoretically allow each neurovascular unit to have independent control of its vascular supply under physiologic conditions.
This parallel organization of the retinal circulation suggested by Nesper and Fawzi has been challenged by Freund and Sarraf [
31] who have suggested a predominantly series-based arrangement of the retinal circulation, with the bulk of the venous drainage of the retina originating at the level of the DCP. The presence of collateral vessels in the setting of retinal venous occlusive disease at the level of the DCP, but not at the SCP, would appear to support this contention.
Recently, using a full-spectrum probabilistic OCTA with a novel algorithm for three-dimensional projection artifact removal (PAR), Hirano and colleagues [
39] investigated the retinal microcirculation. Since full-spectrum OCTA algorithms improve axial resolution, the authors provided important insights into the three-dimensional architecture of the retinal vasculature. Remarkably, unlike the MCP and DCP, the location of the SVP significantly varied among retinal regions. In all parafoveal regions tested, the SVP was featured by a small peak at the NFL-GCL junction and a larger, broader peak within the GCL. Conversely, the perifovea had only a single SVP peak. Furthermore, this peak was closer to the ILM in the perifoveal nasal, superior, and inferior quadrants. The authors presumed that this displacement was secondary to the thicker NFL associated with the arcuate and papillo-macular bundles in these regions.
The nerve fibers in the retina are unmyelinated and they thus require large amounts of energy to maintain ion concentration gradients [
40]. The retinal nerve fiber layer contains the radial peripapillary capillary network to supply oxygen and metabolites to the optic nerve axons. The RPCP is composed of long, straight vessels with few apparent feed points and anastomoses [
32]. These capillaries arise from peripapillary retinal arterioles, extend radially from the optic disc in parallel with the nerve fiber axons, farthest along the temporal arcades [
41].
Using widefield OCTA, Jia and colleagues [
42] examined the RPCP flow characteristics in ten eyes of ten healthy patients and illustrated an association between perfusion in this vascular network and nerve fiber layer thickness. The perfusion of these regions may thus serve as a surrogate measure for the metabolic activity of the ganglion cell axons.
The Choriocapillaris
Given that previous imaging techniques have significant limitations for the evaluation of the CC, OCTA has evolved into a key technology for investigation of the CC [
2,
25,
26].
En face OCTA images of the CC are generated by segmenting a thin slab with a thickness of 10–30-µm starting at Bruch’s membrane. In these OCTA CC en face images, small dark regions (called flow voids or signal voids) [
43,
44] alternate with granular bright areas, the latter thought to represent CC flow, and the former more likely to be secondary to CC vascular dropout or flow reduction [
44]. Signal voids seem to represent the inter-capillary spaces which have been characterized in histological studies on the CC [
45].
However, histological images of the CC are slightly similar to the OCTA versions. With more advanced OCTA technology, we expect to have an improved and more truthful visualization of the CC. However, an enhanced visualization of the CC network may even be obtained with commercially available devices using multiple en face image averaging [
46]. The registration and averaging of sequential en face OCTA images was shown to transform the poorly defined granular appearance of the CC displayed with OCTA into a morphologic pattern that more closely represented the meshwork pattern observed on histology. Notably, not only did averaging improve CC visualization, but more precise quantitative measures of the CC were obtained.
In the CC OCTA images, the number and size of the signal voids have been shown to follow a mathematical relationship of a power law: log (number of signal voids) equals a scaling factor times the log (size of signal voids) plus a constant [
47]. The presence of a power law relationship presumes that the CC is characterized by a propensity for capillary segments to be affected in the vicinity of an already nonfunctional segment.
As explained above, OCTA is still limited in the visualization of the medium- and larger-sized choroidal vessels. This limitation is mainly secondary to scattering by the pigment in the RPE and by the vessels in the CC, and consequent signal attenuation. Recently, Maruko and colleagues [
48] used an SS OCTA device to image the choroid in healthy subjects, and subsequently employed a novel algorithm to improve the visualization of the choroidal vessels. They demonstrated that removal of the projection artifacts of CC can make the choroidal blood flow visible. Importantly, the choroidal blood flow area was correlated with choroidal thickness.