AMD pathogenesis, progression, and prognosis [2, 36–38].
OCTA, as an extension of OCT, has further allowed for the analysis of associated microvascular changes. OCTA allows for depth-resolved visualization of retinal and choroidal vasculature. It acquires repeated B-scans at a given location and assesses differences in phase and intensity between consecutive scans caused by erythrocyte movement, using these decorrelation signals to generate a vascular map co-registered with structural data [39, 40]. En face images generated from axial cuts in the volumetric cube scan allow for the evaluation of various retinal layers, ranging from the internal limiting membrane to the choroid. The thickness and axial position of these slabs can also be altered to best visualize certain pathologies, offering a direct view of the suspected area of disease. The 840-nm wavelength of SD-OCTA limits our visualization of choroidal vasculature, as scattering by media opacities limits penetration below the RPE. This becomes significant when assessing eyes with dry AMD, as drusen contribute to light attenuation, thereby making it difficult to discern whether an underlying decrease in OCTA signal is due to limited signal penetration or is an indication of pathological decreased CC flow. However, this distinction can be made by comparing the en face OCT intensity image, or comparing a cross-sectional B scan image at the area of interest to the en face OCTA image. An area of shadowing, due to signal attenuation, will appear dark on both en face images as well as on the B scan image, while an area of decreased blood flow will appear dark only on the en face OCTA image and normal on the OCT intensity en face and B scan image [9]. However, the longer 1,050-nm wavelength of SS-OCTA allows for increased depth penetration with less scattering and interference, and therefore improved imaging of the choroid and CC [16].
OCTA images of the CC in normal eyes depict a dense, homogenous, and regular vascular pattern. Compared to age-matched normal eyes, OCTA images of eyes with early AMD have shown a reduction in CC density (Fig. 1). This finding supports histologic quantification studies that have shown a correlation between increased drusen density and decreased CC vascular density [8–10]. Focal areas of CC loss may also occur. As these areas become larger, and advance into areas of atrophy, the area originally occupied by the CC may become occupied by displaced underlying larger choroidal vessels [9]. Hypotheses for this lack of flow seen in the CC include drusen-mediated vascular reduction, decreased CC vessel caliber, decreased CC flow as opposed to a complete lack of flow, or a relationship between vessel walls and drusen (rather than lumen) prompting drusen formation at choriocapillary pillars [3]. Irrespective of the cause-effect uncertainty between drusen formation and CC vascular depletion, drusen have been used as an indirect marker for CC dysfunction [3, 8].
Prior belief held that anatomical thinning of the choroid began after there was progression of disease and RPE dysfunction, giving the impression that the choroid was spared during early AMD. However, the discovery of CC changes associated with drusen, as discussed above, has suggested that choroidal changes may begin earlier than considered [2]. Further studies comparing early and intermediate AMD have found conflicting results with respect to alterations in the superficial and deep retinal plexuses. Some studies suggest that the retinal vasculature is unaffected, while others have shown that the superficial vessel density was decreased in intermediate AMD eyes, suggesting that intraretinal vascular depletion starts at the intermediate stage [2]. These intraretinal vascular changes correlate with thinning of the choroid and of the inner retinal layer, and may be a late response to reduced oxygen demand [2].
OCTA of Late AMD
The advanced presentation of dry AMD is GA (or CRORA), which is characterized by a large well-defined area of loss of the RPE, overlying photoreceptors, and the CC [31]. This atrophy allows for the direct visualization of underlying larger choroidal vessels. OCTA has shown loss of CC flow in these regions and even displacement of underlying choroidal vessels into these CC voids (Fig. 2). Moreover, there also appears to be loss of choroidal vessels in the areas in the immediate perimeter of the GA.
Interestingly, SS-OCTA has demonstrated that while there is true loss of flow in the areas of the CC underlying GA, those areas in the perimeter of the GA which appear to have a lack of flow in the CC are actually areas of slow flow [16, 40]. SS-OCTA has allowed for the development of a technique to detect relative blood flow: variable inter-scan time analysis (VISTA) [40, 41]. Analysis of differences between consecutive OCT B-scans at a specific location provide the OCTA flow signal. If the flow within a particular vessel is slower than the scan time of B-scans in rapid succession, then the B-scans acquired at that location would display no differences, and thus the flow would not be detected. The normal interscan time of consecutive B-scans on SD-OCTA devices is approximately 5 ms, while that of the vertical cavity surface-emitting laser (VCSEL) SS-OCTA prototype is approximately 1.5 ms. Faster scanning speeds of SS-OCTA allow devices to capture more B-scans in rapid succession at a particular location without substantially increasing imaging time. With more B-scans available at a particular location, non-consecutive B-scans can be compared. For example, instead of assessment of the decorrelation signal between consecutive B-scans, the differences between alternate (every other) B-scans, now with an interscan time of approximately 3 ms (doubled from the approx. 1.5 ms of consecutive scans), can be compared [8, 16, 40]. This technique is used in VISTA, which allows for the detection of slower flow speeds by varying the time between consecutively acquired B-scans at the same location, thereby obtaining a different decorrelation signal compared to that generated by the traditional consecutive B-scan interscan time. Consequently, VISTA has been able to decrease the standard OCTA threshold of the slowest detectable flow, as well as vary the fastest discernible flow.
Fig. 2. a SD-OCTA image of a 92-year-old female with advanced dry AMD with GA. The region of GA (yellow contour) depicts a well-defined border between normal CC around the GA lesion and loss of CC within the lesion itself. Underlying larger choroidal vessels, which have likely migrated upwards, are clearly visualized. b The corresponding structural B-scan shows increased choroidal light penetration in this region due to RPE loss.
VISTA has helped improve our understanding of GA by allowing for better visualization of slow flow in the CC,
