FLUORESCEIN ANGIOGRAPHY: HYPOFLUORESCENCE

Hypofluorescence may be defined as a lack of fluorescence at any given time in the fluorescein angiogram. Hypofluorescence may be the result of either blocked fluorescence or reduced perfusion. Correlation with the clinical examination can often help differentiate the cause. If the area of hypofluorescence seen on the fluorescein angiogram is similar in shape and size to an ophthalmoscopically visible abnormality, such as hemorrhage or pigment, then blocked fluorescence is likely present. Alternatively, if no such material is present ophthalmoscopically, the hypofluorescence is likely due to hypoperfusion.

Hypofluorescence produced by blocked fluorescence results from a condition that reduces the normal retinal and/or choroidal fluorescence. An example of blocked fluorescence is the dark macular region in the normal angiogram that anatomically represents the higher density of melanin in the retinal pigment epithelium of the macula. Blocked fluorescence may also be caused by opacities in the vitreous cavity, preretinal hemorrhage, intraretinal hemorrhage, subretinal hemorrhage, cotton wool spots, dense hard exudates, choroidal nevi or melanoma, retinal pigment epithelial hypertrophy, and a variety of other retinal disorders.

Angiographic characteristics of blocked fluorescence may help localize the pathologic condition to a particular anatomic level. Large retinal vessels and precapillary arterioles are located in the inner retina, at the level of the nerve fiber layer. Capillaries and postcapillary venules are located in the vicinity of the inner nuclear layer, deeper in the retina. Therefore, a blocking abnormality located anterior to the nerve fiber layer will preclude fluorescence from both the inner and outer layers of the retina as well as from the choroidal circulation. Preretinal hemorrhage is an example of this type of blocked fluorescence. A blocking abnormality such as an intraretinal hemorrhage that occurs deep to the nerve fiber layer but anterior to the inner nuclear layer, where the smaller retinal vessels are located, will block fluorescence from the smaller retinal vessels and choroid but not from the larger retinal vessels. Flame-shaped hemorrhages in the nerve fiber layer block underlying fluorescence from the small retinal vessels and choroid but are often not dense enough to completely block fluorescence from the larger retinal vessels. An abnormality in the outer retina or subretinal space can eliminate or reduce choroidal fluorescence, but allow retinal fluorescence

to be fully visible. Hemorrhage, pigment, turbid fluid, or dense hard exudate that is located in the deep retina or subretinal space may result in blocked choroidal fluorescence.

Hypoperfusion can produce hypofluorescence as a result of a decrease or absence of retinal and/or choroidal blood flow. Hypofluorescence produced

by the absence or decrease of retinal vessels may be readily identified by fluorescein angiography, as these vessels are normally prominent and easily visible. Hypofluorescence may be identified as choroidal in origin when it occurs in the presence of a normal retinal filling pattern. Stereoscopic fluorescein angiography is useful in spatially separating the plane of the retina from the choroid to determine the anatomic location of the hypofluorescence.

Common causes of retinal hypoperfusion include central and branch retinal arterial occlusions and ischemic disease due to diabetes and other causes. Choroidal hypoperfusion may be produced by ophthalmic artery occlusion, giant cell arteritis, hypertensive choroidopathy, lupus choroidopathy, and a variety of other disorders. Patchy choroidal fluorescence is a form of choroidal hypoperfusion that occurs as a normal physiologic condition in some individuals. This phenomenon is the result of the lobular nature of the choriocapillaris. The prechoriocapillaris arterioles are end-arterioles that terminate in a choriocapillaris lobule without anastomoses to adjacent arterioles or lobules. Each lobule fluoresces in an irregular, sometimes hexagonal patch. Some patches fill later than others, resulting in focal areas of patchy choroidal hypofluorescence. These hypofluorescent patches fill normally 2 to 5 seconds later. Defects due to hypoperfusion are best noted in the early phases of the angiogram, as adjacent perfused choroidal

vessels leak dye into the area of hypoperfusion in the late phases.

Normal hypofluorescence of the macula results from several factors including the presence of xanthophyll pigment, the foveal avascular zone, and taller, more pigmented retinal pigment epithelial cells.

Blocked fluorescence may result from hemorrhage or melanin pigment. This angiogram of a patient with exudative age-related macular degeneration demonstrates hypofluorescence corresponding to subretinal blood.

Normal hypofluorescence may occur as patchy filling of the choroid. This early hypofluorescence is observed commonly in the early phase of fluorescein angiography, and normalizes in the later phases of the angiogram.

Traumatic choroidal rupture may be associated with subretinal hemorrhage. The normal retinal vessels overlying the blocked, hypofluorescent area confirm the subretinal location of the hemorrhage. The choroidal rupture is the hyperfluorescent lesion concentric to the optic disc.

Diabetic retinopathy may be associated with capillary nonperfusion in the macula and peripheral retina. In this angiogram, the foveal avascular zone is enlarged, and the temporal macula has significant capillary dropout.

This patient with a Purtscher’s-like retinopathy has marked hypofluorescence due to nonperfusion throughout the posterior fundus resulting from occlusion of the retinal capillaries.

Fluorescein angiogram of a patient with age-related macular degeneration demonstrates a large blocked area of hypofluorescence corresponding to a subretinal hemorrhage. Note the retinal vessels over the area of hypofluorescence fill normally, confirming the subretinal location of the blood.

Fluorescein angiogram of a patient with a macular branch retinal vein occlusion. The superficial flameshaped hemorrhages within the nerve fiber layer block both retinal and choroidal fluorescence.

Vitreous and preretinal hemorrhage in a patient with proliferative diabetic retinopathy. Note how the preretinal hemorrhage blocks the underlying optic disc and retinal vessels.

Stargardt disease is characterized by a “silent” choroid on fluorescein angiography. The lipofuscin-packed retinal pigment epithelial cells block the underlying choroidal fluorescence. The central bull’s-eye pattern of hyperfluorescence results from retinal pigment epithelial atrophy.

The stippled pattern of hypofluorescence in this patient with age-related macular degeneration results from blocking by focal areas of retinal pigment epithelial hyperpigmentation.

This patient has numerous hypofluorescent spots corresponding to the location of multifocal vitelliform lesions that block fluorescence in the early phases of the angiogram.

Branch retinal vein occlusions may be associated with capillary nonperfusion. Note the hypofluorescence in the fovea and inferior macula.

Fluorescein angiography in patients with acute posterior multifocal placoid pigment epitheliopathy is characterized by a “block early, stain late” pattern. The hypofluorescent areas seen in the early phase of the angiogram may result from choroidal nonperfusion.

This patient with an ischemic central retinal vein occlusion demonstrates hypofluorescence resulting from intraretinal hemorrhages and profound capillary nonperfusion.

Choroideremia is characterized by loss of the retinal pigment epithelium and choriocapillaris. Loss of the choriocapillaris results in hypofluorescence due to nonperfusion. The larger choroidal vessels are visible in the areas of atrophy.

This patient has a well-defined hypofluorescent spot due to nonperfusion following laser photocoagulation for exudative age-related macular degeneration. Intense laser photocoagulation obliterates the choroidal circulation.

This fluorescein angiogram demonstrates hypofluorescence as a result of retinal capillary nonperfusion and laser photocoagulation. Laser burns may become hyperpigmented over time, resulting in blockage of the normal choroidal fluorescence.