Age-related macular degeneration (AMD) may be divided into two types. Nonexudative (“dry”) AMD has several morphologic forms, including “hard” discrete drusen, shallow retinal pigment epithelial detachments associated with thickened Bruch’s membrane (“soft” drusen), and geographic atrophy (GA) of the retinal pigment epithelium (RPE).³ On FA the area of GA appears hyperfluorescent for window defect from the early frames of the angiogram, with late staining of the underlying sclera (Fig. 1). However, these pathologic changes can usually be assessed by clinical examination, and FA is generally not necessary to diagnose nonexudative AMD. An exception is cuticular drusen, which may appear clinically as a subtle disturbance of the RPE; FA reveals multitudes of small, discrete drusen described as “stars in the sky” (Fig. 2). The second type of AMD, which is associated with soft drusen, is known as exudative (“wet”) AMD. It is due to a choroidal neovascular membrane that has incompetent vessels resulting in detachments of the RPE and the neurosensory retina. Consequently, in patients with a large RPE and/or serous neurosensory detachment, FA is often necessary to rule out a choroidal neovascularization (CNV). In general, a small pigment epithelium detachment (PED) and a larger neurosensory detachment overlie CNV, while the opposite is generally the case in a nonexudative PED. Additionally, CNV often presents as a “notched” PED (Fig. 3).⁴ The presence of subretinal blood or pigment at the border of a PED strongly indicates that the detachment is exudative in origin (Fig. 4). Similarly, a rip in the RPE generally reflects subretinal fibrosis from a CNV (Fig. 5 and 6). The diagnosis is more difficult in patients who have a chronic, organized PED. Such a lesion may be due to either nonexudative AMD or to an organized, fibrotic CNV. Clinically and angiographically, it may be impossible to distinguish between these two conditions. In most cases, however, FA does assist in making the diagnosis.

In patients with a shallow neurosensory detachment, the Amsler grid test and visual acuity may be normal. If there is subtle elevation of the neurosensory retina on biomicroscopy examination, FA may demonstrate a CNV before it is symptomatic. It is often easier to evaluate both RPE and neurosensory detachments with good stereoscopic FA pictures than with direct examination.⁵ Consequently, FA can be helpful in determining the presence and extent of these processes. This is particularly important in patients with CNV due to AMD, because its aggressive course often requires prompt intervention to save central vision.^6,7

Furthermore, FA helps in recognizing two types of CNV: classic and occult. Classic CNV consists of a well-defined neovascular membrane, which is apparent in the early phase of the angiogram and shows late leakage of dye beyond its boundaries (Fig. 7 and 8). Occult CNV is seen on by FA as an area of late hyperfluorescence of undefined origin or as a neovascularized PED (Fig. 9 and 10). Mixed-type CNV is predominately classic or minimally classic depending on whether the classic component is more or less than 50% of the entire lesion (Fig. 11).

FA is also useful in characterizing two other subgroups of CNV: retinal angiomatous proliferation (RAP)^{8,9,10,11,12,13,14,15,16} and polypoidal choroidal vasculopathy (PCV).^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50} RAP begins in the deep retinal complex, forming intraretinal neovascularization (IRN), which may subsequently progress to extend beneath the neurosensory retina, forming subretinal neovascularization (SRN), and a vascularized PED.⁸ In the later phases of the process there may be a retinal-choroidal anastomosis (RCA). Clinical features of RAP include intraretinal hemorrhages, cystoid macular edema, and associated vascularized PED. FA is useful in revealing the presence of the angiomatous intraretinal vascular complex and the extension of the associated PED (Figs. 12 and 13). However, other diagnostic techniques such as indocyanine green (ICG) angiography, and optical coherence tomography (OCT) may be able to better demonstrate the presence of the RAP lesion.

PCV is characterized by the presence of dilated, choroidal vascular channels ending in orange bulging polyp-like dilations in the peripapillary and macular area. Associated features are recurrent subretinal hemorrhage and vitreous hemorrhage, relatively minimal fibrous scarring, absence of retinal vascular disease, pathologic myopia, and signs of intraocular inflammation. FA demonstrates the presence of the dilated vascular channel (Fig. 14 and 15). However, the presence of blood and exudation may block the details of the choroidal circulation on the angiogram. In these cases, ICG angiography can better demonstrate the presence of a distinct network of vessels within the choroid because the larger choroidal vessels are filled with dye.

The FA can also distinguish CNV from simulating lesions. For example, a dark mound of blood due to hemorrhage from a CNV will block choroidal fluorescence, whereas vascular tumefactions such as choroidal hemangiomas leak fluorescein. Choroidal melanomas frequently block early choroidal fluorescence and then leak fluorescein from their intrinsic vascular network in later phases of FA.

Central serous chorioretinopathy (CSC) is characterized by breakdown of the outer retinal barrier, with leakage of fluid through a defect in the retinal pigment epithelium into the subretinal space, resulting in a serous neurosensory detachment.^{78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205} The ophthalmologist can usually diagnose CSC based on the clinical examination and demographic information.^93,94,95 Most patients with CSC are middle-aged men⁷⁴ who often have type A personalities.^{75,96,97,98,99,100,101,102,103,104} CSC has also been associated to the use of corticosteroids,^{105,106,107,108,109,110,111,112,113,114,115,116,117,118} pregnancy,^{119,120,121,122,123,124,125,126} increased adrenaline level and stress,^{127,128,129,130,131,132} hemodialysis,^133,134 collagen vascular diseases,^{135,136,137,138,139,140,141,142,143,144,145,146,147} and hypertension.^{148,149,150,151,152,153,154,155,156,157} CSC typically presents as a large serous detachment in the posterior pole without an obvious source of the subretinal fluid.⁷⁶ However, because a small CNV cannot be ruled out, FA is usually done to confirm the diagnosis. Characteristically, there is a small RPE defect, which hyperfluoresces early, and then there is slow filling of the overlying neurosensory detachment, which may have a classic “smokestack” (Fig. 21) or “ink blot” (Fig. 22) appearance.^{158,159,160,161} Occasionally, FA demonstrates multiple sites of leakage (Figs. 23, 24, and 25). FA sometimes fails to distinguish CSC from CNV readily because fibrinous subretinal precipitates can cause slow filling of the RPE detachment, which is suggestive of CNV (Fig. 26). Sometimes peripapillary PCV can cause a neurosensory macular detachment masquerading as CSC (Fig. 27).⁷⁷