Page 248 - Computational Retinal Image Analysis

246 CHAPTER 13 Drusen and macular degeneration

no treatments that can halt or reverse the progression of advanced non-neovascular
AMD, a number of candidate therapies are in development. When treatment becomes
available, detection and monitoring of disease progression will be important in rou-
tine clinically practice.

2 Histopathological lesions and clinical classification

A spectrum of degenerative diseases (including both inherited and acquired patholo-
gies) affects the macula. This chapter focuses on image analysis in AMD: the most
common of these entities. Many of the pathological features of AMD are common to
other disease states, for example choroidal neovascularization. However, the appear-
ance on imaging of individual lesions is characteristic of particular disease states, in
part due to associated pathology in neighboring tissues such as the retinal pigment
epithelium (RPE).
2.1 Normal aging of the macula

AMD must be differentiated from normal aging of the macula. This distinction causes
difficulties in the classification of AMD. The retina (and central nervous system) are
comprised of cell types that do not undergo renewal with mitotic division; these
tissues are particularly prone to age-related changes. The choriocapillaris, Bruch’s
membrane and RPE provide anatomical and metabolic support for the photorecep-
tors. With age, rod and cone photoreceptor outer segments become disrupted [12].
Outer segment material accumulates adjacent to the RPE apical surface and lipofus-
cin is deposited in cone inner segments [13].
Cumulative damage to the RPE with age leads to impairment of phagocytosis
and molecular degradation of photoreceptor outer segments. Progressive accumu-
lation of lipofuscin causes the RPE cells to enlarge [14]; there is patchy deposi-
tion of material termed basal laminar deposits between the RPE and its basement
membrane [15, 16]. Bruch’s membrane thickens with age due to deposition of
membrane-bound bodies, collagen and mineralized deposits [16]. Even with nor-
mal aging, the presence of a small number of drusen is evident histologically. The
density and diameter of the choriocapillaris decreases with age resulting in a reduc-
tion in choroidal thickness [17].

2.2 Lesions of non-neovascular AMD
The principle histopathologic features of AMD are degeneration of the RPE and pres-
ence of membranous debris and extensive basal laminar deposits [18]. Enlarged RPE
cells with increased pigmentation and deposited lipofuscin are visible clinically as
focal areas of hyper- or hypopigmentation. Progressive disorder of the RPE is ac-
companied by loss of photoreceptors and reduction of nuclei in the outer nuclear layer
(ONL); necrotic, hyperpigmented portions of cells containing membrane-bound gran-
ules are released into the sub-RPE and sub-retinal space. Generalized thickening of
Bruch’s membrane is accompanied by focal areas of thinning and small breaks [19].