Fluorescein angiography of a typical choroidal nevus with bland surface features (see Fig. 1) shows the entire lesion to be hypofluorescent relative to the adjacent uninvolved choroid throughout the study. No large-caliber choroidal blood vessels are usually identifiable within the lesion. The retinal vasculature overlying the lesion appears well defined and normal on fluorescein angiography.

ICG angiography of a typical melanotic choroidal nevus (see Fig. 2) shows better definition of the basal area of the lesion than does fluorescein angiography. The entire lesion appears completely and uniformly dark throughout the ICG angiogram. Only the larger retinal blood vessels overlying the nevus are usually demonstrated on ICG angiography.

Approximately 10% to 15% of choroidal nevi are largely or completely amelanotic clinically. Fluorescein and ICG angiography of an amelanotic choroidal nevus (see Fig. 3) tend to show less prominent hypofluorescence of the lesion than they do with darkly melanotic nevi. Because of the lack of intracellular melanin pigment within the nevus cells, some large-caliber choroidal blood vessels running through the nevus may be visible in the region of the mass (see Fig. 3B and C). These choroidal blood vessels are better defined by ICG angiography than by fluorescein angiography. Amelanotic choroidal nevi often appear mildly hyperfluorescent in late-phase frames (see Fig. 3D).

If a choroidal nevus has drusen and RPE alterations on its surface (see Fig. 4A), fluorescein angiography (Fig. 4B, C, and D) tends to show patchy or stippled window defect hyperfluorescence corresponding to foci of RPE depigmentation, fluorescence blockage by clumps of RPE hyperplasia on the surface of the lesion, and late staining of at least some of the drusen. These features are not usually as evident on ICG angiography as they are on fluorescein angiography.

Small melanocytic choroidal tumors larger than 5 mm in diameter and thicker than 1 mm but without clearly invasive clinical features (e.g., nodular eruption through Bruch’s membrane, retinal invasion) may be either benign nevi or small choroidal melanomas. Several features of these lesions have been identified as prognostic of the likelihood of subsequent lesion enlargement,¹³ a surrogate indicator of the malignant potential of the tumor. Features suggestive of low growth potential and probable benign histology include thickness less than or equal to 1.5 mm, uniform gray-brown coloration of the lesion, and drusen and RPE clumping on the surface of the lesion. In contrast, features suggestive of higher growth potential and probable malignant histology include thickness greater than 1.5 mm, nonuniform coloration of the lesion, prominent clumps of lipofuscin pigment on the surface of the lesion, and serous subretinal fluid overlying and surrounding the lesion. None of these features is a reliable indicator of the underlying histologic nature of the tumor; however, the greater the number of unfavorable features, the greater the likelihood of lesion enlargement if it is followed without treatment after initial detection.

Several authors have evaluated fluorescein and ICG angiography as differential diagnostic tools for differentiating between large benign choroidal nevi and small malignant choroidal melanomas.^9,10 An example of such a lesion evaluated by fluorescein angiography is presented as Figure 5. Some common assertions based on these studies include the following. If the lesion is a nevus, fluorescein angiography is likely to show hypofluorescence of the lesion throughout the study, absence of large-caliber intralesional blood vessels, and lack of late smudgy hyperfluorescence resulting from leakage from these vessels. In contrast, if the lesion is a melanoma, fluorescein angiography is likely to show at least some intralesional tumor blood vessels, some patchy or smudgy fluorescein leakage from those blood vessels, and at least patchy or smudgy late fluorescence of the tumor. ICG angiography is more likely to reveal intralesional blood vessels within bland appearing small melanocytic choroidal lesions (especially darkly melanotic lesions) than is fluorescein angiography, and lesions with prominent intralesional blood vessels are generally regarded as more likely to be melanomas. Unfortunately, there have been no confirmatory angiographic-histopathologic correlation studies of small melanocytic choroidal tumors in the nevus versus melanoma category to confirm or refute these assertions. At best, this author regards the fluorescence angiographic features of bland appearing small melanocytic choroidal tumors as suggestive but not confirmatory of the pathologic nature of the tumor.

If one obtains a fluorescein angiogram on a small melanotic choroidal lesion (nevus versus melanoma) that has prominent clumps of lipofuscin pigment on its surface (Fig. 6), the pigment clumps appear intensely hypofluorescent throughout the study. This appearance is attributable to the complete blocking of choroidal fluorescence by the lipofuscin. ICG angiography does not show lipofuscin pigment clumps on the surface of the tumor as well as fluorescein angiography does.

A blister of serous subretinal fluid sometimes develops over and around a presumed choroidal nevus (Fig. 7A), especially if the lesion is located in the macula.¹¹ If one performs a fluorescein angiogram on a small melanocytic choroidal lesion (nevus versus melanoma) that has shallow overlying serous subretinal fluid (see Fig. 7B, C, and D), one or more hyperfluorescent leak sites may show up slowly at the RPE level as the study progresses. In some cases, fluorescein will clearly leak from those foci into the overlying serous subretinal fluid. ICG angiography does not show hyperfluorescent leak sites at the RPE level as well as fluorescein angiography does.

A choroidal neovascular membrane occasionally develops from the surface of a small melanocytic choroidal tumor (nevus versus melanoma).¹² This vascular structure can usually be anticipated because of the presence of ophthalmoscopically evident hemorrhagic or exudative subretinal fluid overlying a portion of the tumor (Fig. 8A). Fluorescein angiography in such cases (see Fig. 8B to D) generally reveals the neovascular membrane as a relatively well-defined vascular network that fluoresces brightly in the early frames of the study and leaks progressively by the late frames. If the subretinal fluid is grossly hemorrhagic, ICG angiographymay show the choroidal neovascular network better than does fluorescein angiography.

Small melanocytic choroidal lesions in the nevus versus melanoma category are frequently monitored periodically following initial documentation for enlargement or other indicators of possible malignant behavior. Fluorescein angiography sometimes defines the basal area of these lesions better than does fundus photography, but ICG angiography is clearly the preferred technique for this purpose. If one elects to follow a small melanocytic choroidal tumor without treatment, comparative fluorescence angiography can be used to identify slight lesion enlargement that is not clearly evident by ophthalmoscopy or comparison of fundus photographs. Because benign choroidal nevi can and do enlarge, however, detection of subtle lesion enlargement by fluorescence angiography probably has limited differential diagnostic value in these lesions.

The typical choroidal melanoma that has not broken through Bruch’s membrane generally appears as a gray-brown to dark brown, dome-shaped, solid choroidal mass (Fig. 9A). The overlying retina commonly appears normal except that it is draped over the choroidal tumor. Fluorescein angiography (see Fig. 9B, C, and D) typically shows the tumor to be relatively hypofluorescent during the early frames of the study. If prominent clumps of orange lipofuscin pigment are present on the surface of the tumor, they will appear intensely hypofluorescent throughout the study because of blockage of the underlying choroidal and tumor vascular fluorescence. During the arterial phase frames of the study, several ill-defined large-caliber deep intralesional blood vessels may be identifiable against the generally hypofluorescent background. As the study continues, these large intralesional blood vessels leak progressively so that the surface of the lesion tends to appear hyperfluorescent by the late frames. Fluorescein may also accumulate in the overlying retina and retinal pigment epithelium as tiny discrete pinpoint foci of intense hyperfluorescence. If serous retinal detachment is present overlying and around the tumor, the fluorescein will leak through the retinal pigment epithelium and accumulate in the subretinal fluid by the late frames. The retinal vascular pattern of the overlying retina commonly appears unremarkable in these cases.

If ICG angiography is performed on a similar tumor (Fig. 10), the tumor mass generally appears more intensely hypofluorescent throughout the study and its intrinsic blood vessels appear more clearly visible than on fluorescein angiography. ICG slowly accumulates within the extracellular space of the tumor so that the tumor usually appears mildly hyperfluorescent, at least in part, in the late frames.

If the choroidal melanoma being evaluated is relatively amelanotic (Figs. 11A and 12A), its large-caliber intralesional blood vessels will tend to show up more distinctly on both fluorescein angiography (see Fig. 11B, C, and D) and ICG angiography (see Fig. 12B, C, and D) than they would in a darkly melanotic choroidal melanoma. Despite its amelanotic color, the cellular component of the mass tends to be at least mildly hypofluorescent relative to the adjacent uninvolved choroid during the early frames of the study. As with melanotic melanomas, the mass usually appears at least mildly hyperfluorescent in the late-phase frames (see Figs. 11D and 12D).

If a choroidal melanoma has erupted through Bruch’s membrane (Figs. 13A and 14A), it forms an apical nodule that is generally hypomelanotic and contains many large-caliber blood vessels. Fluorescein angiography of these tumors (see Fig. 13B, C, and D) typically shows hypofluorescence of the base of the lesion during the early frames, relatively rapid filling of the prominent blood vessels in the apical nodule during the venous and recirculation frames, and intense late staining of the apical nodule resulting from progressive fluorescein leakage by the late-phase frames. Similarly, ICG angiography of these tumors (see Fig. 14B, C, and D) also shows relative early hypofluorescence of the tumor base, early filling of prominent intralesional blood vessels within the apical nodule, intense staining of the apical nodule by the recirculation phase frames, and persistent late hyperfluorescence of the mass.