Page 249 - Computational Retinal Image Analysis

2 Histopathological lesions and clinical classification 247

Drusen are the characteristic clinical feature of AMD. They consist of extracel-
lular hyalinized material deposited between the basement membrane of RPE cells
and Bruch’s membrane. Drusen can be described in terms of size, color, morphology
and extent. The size of a druse is estimated by comparing its shortest diameter to the
width of a major retinal vein as it crosses the edge of the optic disc (approximately
125 μm). Small drusen are <63 μm (less than half the width of a vein); medium 63
to 125 μm and large ≥125 μm [20]. More precise measurements are possible with
digital software. Drusen vary in color from bright yellow to white. Drusen morphol-
ogy can be divided into hard and soft groups (differing in their relative proportions of
component material). Soft drusen are usually medium size or larger, have an amor-
phous appearance and may converge. Hard (nodular) drusen are generally small and
exist separately from one another. The extent or severity of macular involvement may
be assessed by counting drusen or estimating the total macular area occupied [21].
Drusen may grow larger in diameter and height and may coalesce. Alternatively, they
may spontaneously regress which may be accompanied by neighboring RPE and
photoreceptor atrophy.
The principle clinical characteristic of AMD is the presence of at least one
medium-sized druse or extensive small drusen [22]. On FA small, hard drusen fluo-
resce brightly in the mid-venous phase (demonstrating distinct edges) and fade soon
after. Coalescent small drusen remain fluorescent through the mid-phase followed
by late fading [23]. Soft drusen are not usually hyperfluorescent in the early phases
of FA but become so in the later stages. Small, hard drusen are not evident on indo-
cyanine green (ICG) imaging; soft drusen are hypofluorescent and show a hyper-
fluorescent margin in the late phase [24]. Unless there are changes in the overlying
RPE, small drusen are not seen on autofluorescence (AF) imaging (see Fig. 1(ii)).
Soft drusen may demonstrate mild hyperautofluorescence. On optical coherence to-
mography (OCT) imaging, small drusen appear as slight elevations of the RPE (see
Fig. 1(iii)). Soft drusen are seen as 63–1000 μm deposits posterior to the RPE of low,
high or, most commonly, intermediate reflectivity [25]. Changes to the neurosensory
retina are common anterior to drusen including thinning of the photoreceptor layer,
variable alterations in the ellipsoid zone and hyperreflective foci [26].
Other patterns of drusen are seen in non-neovascular AMD. Subretinal drusenoid
deposits (SDD, reticular drusen, reticular pseudodrusen) are seen as pale yellow de-
posits approximately 250 μm in diameter forming a network at the macula but spar-
ing the fovea (see Fig. 2). On color photography, SDD are best seen with blue light.
On AF imaging, the lesions exhibit hypoautofluorescence. OCT imaging demon-
strates cone shaped deposits anterior to the RPE some of which breach the ellipsoid
layer [27]. Basal laminar or cuticular drusen are round, uniform sub-RPE deposits
50–75 μm in size [28]. These lesions exhibit a “saw-toothed” pattern on OCT and are
not part of the AMD spectrum.
Deposits in the subretinal space of extracellular photoreceptor material rang-
ing between 350 and 1760 μm in diameter are referred to as vitelliform lesions (see
Fig. 3). These deposits are part of a spectrum of changes described as pattern dys-
trophy. They are not common in AMD and may indeed represent a separate disease