AMD can be classified into two forms: nonneovascular (dry) and neovascular (wet or exudative). Nonneovascular or dry AMD accounts for 85 to 90% of all cases of AMD. Dry AMD is nearly always bilateral and primarily affects the central area of retina known as the macula. It tends to lead to a gradual but potentially significant reduction in central vision. The visual complications associated with dry AMD increase in severity with age. In the 55- to 65-year age group, only 1% of adults suffer with visually significant disease, compared to 20% in adults older than 75 years.²

6.2 Early Nonneovascular Age-Related Macular Degeneration

Early dry AMD is defined clinically as the presence of numerous small or intermediate sized drusen. Drusen are small yellow amorphous deposits of lipofuscin that lie between the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane. Drusen deposition is the first clinically visible lesion in patients with dry AMD and is likely to represent the complex disruption of the normal anatomy and physiological processes of the eye.

The choroid is composed of five layers, three of which are vascular: the choriocapillaris (CC), Sattler’s layer, and Haller’s layer. The CC, the thin capillary layer of the choroid, is located adjacent to Bruch’s membrane and has a mutualistic relationship with the RPE.^{3,​4,​5,​6} The RPE’s function is to provide nutrients and remove waste products from the overlying photoreceptors.⁶

In dry AMD, it is believed that these anatomical structures are disrupted. There is a gradual destruction of the RPE and the photoreceptor layer, thickening of Bruch’s membrane, and atrophy of the CC so that the underlying choroidal vasculature becomes visible. There is currently no treatment for dry AMD and it can lead to severe visual impairment.

Several grading systems for the dry AMD exist, with the earliest based on color fundus photography. Of these classifications, the AREDS (Age-Related Eye Disease Study) system has been most commonly utilized to document the site and size of the drusen to help track the progression of the disease over time.⁷ Despite fundus photography being readily available, the images only provided two-dimensional data on shape and the spatial location of the drusen and little quantitative data such as change in the drusen volume over time ( ▶ Fig. 6.1a).

The advent of optical coherence tomography (OCT) has greatly improved our understanding of dry AMD. With the use of high-resolution spectral domain OCT (SD-OCT) and swept-source OCT (SS-OCT), it is possible not only to visualize the individual layers of the retina and the choroid, but to also acquire three-dimensional quantitative assessment of the drusen that are associated with early dry AMD.

Drusen are visible on OCT B-scans as hyper-reflective material between Bruch’s membrane and the RPE ( ▶ Fig. 6.1e).^8,​9,​10 Retinal layers overlying drusen show a thinning in the photoreceptor layer in 97% of cases. It is also noted that the average photoreceptor layer thickness was reduced by 27% when overlying drusen compared to similar sites in normal age-matched control eyes. The inner retinal layers usually remain unchanged. These findings demonstrate a degenerative process with photoreceptor loss leading to visual impairment.¹¹

6.3 Optical Coherence Tomography Angiography in Dry AMD

Optical coherence tomography angiography (OCTA) enables rapid, noninvasive, and depth-resolved imaging of the retinal and choroidal vasculature, by detecting the motion contrast from flowing blood.^{12,​13,​14} OCTA images are generated when multiple B-scans are acquired in rapid succession from the same anatomic location. Stationary tissue produces a nearly constant scattering of the OCTA signal, whereas moving tissue such as blood produces an OCTA signal that changes over time. This signal decorrelation is portrayed as a grayscale image where pixels from stationary tissue appear black and pixels from moving tissues appear white. Structural and angiographic datasets can be simultaneously acquired and co-registered, allowing for concurrent visualization of the three-dimensional structure of the vasculature and blood flow.^{15,​16,​17}

Angiography is not a new technique; however, the current gold standard imaging modalities, FA and indocyanine green angiography (ICGA), have inherent flaws in their ability to image the CC. The image quality of FA is reduced by the absorption of the blue-green excitation wavelength of fluorescein by macular xanthophyll and the RPE. The fine microvascular network of the choroid is further obscured by leakage of approximately 20% of the fluorescein dye that fails to bind to albumin, causing an early hyperfluorescence.¹⁸ Conversely, ICGA, which is considered the superior modality for imaging the choroid, has not gained widespread acceptance as it is not depth-resolved, so separating the CC blood flow from the deeper choroidal vasculature is a complex task.^19,​20 In addition, these modalities are invasive, involving the use of intravenous contrast that can result in systemic side effects, such as nausea, vomiting, and, rarely, anaphylaxis.^{21,​22,​23}

OCTA is a noninvasive, nontouch technique and does not require the injection of intravenous dye. This is the key to its use in dry AMD because it means it can be utilized repeatedly in follow-up appointments to track the anatomical disruption of the CC vasculature in patients with early dry AMD as it progresses to late-stage AMD. Despite its huge potential, OCTA is not without drawbacks. OCTA uses volumetric data ( ▶ Fig. 6.2) to assess blood flow and as such requires increased scanning speeds to acquire this data. This not only increases the time taken to image patients, but also means a reduced scanning field compared to the traditional angiography. This may not, however, be as much of a drawback in AMD where the area of interest is primarily the macula.

En face OCTA permits evaluation of the individual layers of the retina that can be correlated and cross-registered with structural OCT scans ( ▶ Fig. 6.2b). Using this methodology, it is possible to plot the topological location of the drusen and to compare this with the underlying CC ( ▶ Fig. 6.1 and ▶ Fig. 6.3). It has been noted that in early dry AMD, some drusen may be spatially related to areas of focal CC loss and that patients with Dry AMD have a general reduction in CC density compared to age-matched controls ( ▶ Fig. 6.1c,d). This research is supported by histological data that suggest that drusen often form at the sites of reduced CC density.^{5,​24,​25,​26,​27} However, since OCTA shows areas of CC void even in normal individuals, it is not quite clear if the changes seen under some drusen represent true CC loss or an incidental intersection of areas of thinned CC with the presence of drusen.

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