this middle phase that hyperfluorescent lesions start to become more evident. In the late phase, which occurs around the 15 min time point, no details of the retinal or choroidal vessels are visible. The large choroidal vessels become hypofluorescent, the optic disc appears dark, and background fluorescence is significantly diminished, all of which allow choroidal vascular abnormalities such as choroidal neovascular membranes to stand out markedly (Fig. 4.7).

Certain terms in fundus angiography relate specifically to ICG imaging. A distinct focus of increasing hyperfluorescence less than one disc diameter in size is referred to as a “hot spot”. Hot spots typically represent an area of occult CNV, or polypoidal vasculopathic abnormalities (Fig. 4.8). Another term that is used to describe occult CNV is “placoid hyperfluorescence,” which applies to an area of hyperfluorescence that is greater than one disc diameter in size and lacks well-defined borders. These terms reflect the utility of ICG angiography for cases in which occult recurrent or persistent CNV is suspected, but the fluorescein angiography is equivocal.

Non-neovascular Age-Related

Macular Degeneration

Drusen

Drusen have been classified into a number of groups on the basis of size and appearance. They may be large (>125 m(mu)m, about the diameter of an arcade vein near the optic disc) intermediate (63–124 m(mu)m), or small (<63 m(mu)m). The RPE overlying a drusen is often thinner, which produces a transmission window defect on FA. Smaller drusen can sometimes appear bright early in a fluorescein angiogram. Basal laminar drusen, or cuticular drusen, appear as a “starry sky” of thousands of bright spots on FA (Fig. 4.9). Occasionally, cuticular drusen may be associated with yellow subfoveal material that mimics vitelliform dystrophy. Soft drusen usually are not readily visible in the early phases of a fluorescein angiogram, but may stain later (Fig. 4.8). Subretinal drusenoid deposits, also known as reticular pseudodrusen, are subretinal drusen that

do not exhibit significant angiographic findings [40]. The biochemical composition of drusen may affect both fluorescein [41] and indocyanine green staining [42].

On OCT, drusen are visualized as moderatelyreflective material under the highly reflective RPE layer. Drusen have a relatively homogeneous composition. Typically, drusen lift up the RPE, and in the case of large soft drusen, Bruch’s membrane may be visualized (Fig. 4.8). Cuticular drusen are apparent as smaller nodular deposits below the RPE, creating a “saw-tooth” pattern. Reticular pseudodrusen may be visualized anterior to the RPE on OCT. On autofluorescence,softdrusenappearhypoautofluorescent, although they may have a hyperautofluorescent rim. Cuticular drusen and reticular pseudodrusen also may be hypoautofluorescent, although many times they are not apparent on fundus autofluorescence [43].

Pigmentary Abnormalities Including

Geographic Atrophy

Focal hyperpigmentation is a risk factor for the development of CNV. Histopathologic correlation of focal hyperpigmentation has demonstrated detached cells containing pigment in the subretinal space. These areas of focal hyperpigmentation also display focal hyperautofluorescence and increased absorption of infrared light, suggesting these cells contain lipofuscin [44]. In addition, the presence of focal hyperpigmentation was found to be highly correlated with retinal angiomatous proliferation in the fellow eye [44]. In cases of focal hyperpigmentation apparent on examination, intraretinal migration of highly-reflective RPE pigment may be visualized on OCT (Fig. 4.4) [45].

Another pigmentary alteration is RPE atrophy, which can occur in sharply-defined areas of severe atrophy, known as geographic atrophy (GA), or in less well-defined, more granular regions of less severe atrophy known as nongeographic atrophy. The outer borders of a region of geographic atrophy are slightly hyperpigmented at the level of the RPE and occasionally hyperautofluorescent [46], suggesting that these cells may contain excess lipofuscin. Of note, areas of

Fig. 4.7 Idiopathic polypoidal choroidal vasculopathy (IPCV). (a) SLO mid-phase fluorescein angiogram from an eye with IPCV. Inferior to the disc, there is a large patch of mottled hyperfluorescence representing mostly RPE atrophy, with pinpoint areas of higher fluorescence possibly representing polypoidal lesions. (b) SLO ICG angiogram more clearly demonstrates a single polypoidal

lesion (arrow) with an adjacent large pigment epithelial detachment (PED). (c) Digital color fundus photograph demonstrates a large hemorrhagic PED as well as a large amount of hard exudates inferiorly. (d) SLO infrared image demonstrates the direction of subsequent OCT image. (e) OCT image clearly demonstrates the presence of a large PED, with a partially-detached posterior hyaloid

Fig. 4.8 Soft drusen. (a) Digital color fundus photograph from an eye soft drusen. (b) Digital red-free image demonstrating a bright appearance of the drusen. (c) Digital fluorescein angiogram demonstrates difficult visualization

of soft drusen. (d) OCT image shows focal elevations of the RPE by homogeneous moderately-reflective drusenoid material, and visualization of the underlying Bruch’s membrane

Fig. 4.9 Cuticular drusen. (a) Digital red-free fundus photograph from an eye with cuticular drusen. (b) SLO fluorescein angiogram demonstrates a “starry-sky appearance, and shows many more drusen than apparent on the

red-free photograph. (c) SLO fundus autofluorescence demonstrates minimal changes in areas with cuticular drusen. (d) OCT shows a “saw-tooth” appearance of the RPE overlying small deposits of drusenoid material

increased hyperautofluorescence at the border of healthy and atrophic RPE represent areas of “sick” RPE at risk for cell death and resultant enlargement of geographic atrophy in the future (Fig. 4.2) [47].

During fluorescein angiography, the appearance early in the fluorescein depends on the amount of retained choriocapillaris. A “window defect” is often apparent in the area of RPE atrophy, with variable appearance of the underlying choroidal vessels. Late in the angiogram, a well-demarcated region of late hyperfluorescence without signs of leakage becomes evident, which is secondary to staining of deeper layers of the eye without normal blockage by overlying pigment. Generally, geographic atrophy shows increasing fluorescence during the early and mid phases of the fluorescein angiogram. More advanced forms of geographic

atrophy show early fluorescence of the larger choroidal vessels with a lack of overlying choriocapillaris. Geographic atrophy often appears hypofluorescent during indocyanine green angiography because of the lack of healthy choriocapillaris and overlying RPE, which shows normal physiologic staining late in the angiographic sequence.

On OCT, areas of RPE atrophy appear as focal thinning of the RPE layer with resulting increased penetration of OCT signal into the underlying choriocapillaris and sclera. Overlying areas of RPE atrophy, the inner retinal layers, including the IS/OS junction as well as the outer nuclear layer, may appear thinned or missing [48]. On occasions, retinal pseudocysts may appear overlying areas of geographic atrophy, which likely represent a degenerative process within the retina [49].