Fundus Autofluorescence in Atrophic Age-Related Macular Degeneration



Fundus Autofluorescence in Atrophic Age-Related Macular Degeneration


Steffen Schmitz-Valckenberg

Monika Fleckenstein

Almut Bindewald-Wittich

Hendrik P.N. Scholl

Frank G. Holz



Atrophic age-related macular degeneration (AMD) represents the late stage of “dry” AMD. It is characterized by the development of atrophic patches, which may initially occur in the parafoveal area (1, 2, 3, 4). These atrophic areas appear funduscopically as sharply demarcated areas of depigmentation through which deep choroidal vessels can be seen. During the natural course of the disease, the areas of atrophy slowly enlarge over time. In atrophic AMD, characteristically, the fovea remains uninvolved until the advanced stages of the disease, a phenomenon referred to as “foveal sparing.” A widely established term used to refer to this advanced form of dry AMD is “geographic atrophy” (GA). By contrast, the term “areolar choroidal atrophy” is usually used to refer to findings that are similar but caused by monogenetic retinal macular dystrophies, which may manifest earlier in life.

Severe visual loss secondary to GA occurs in about 20% of all patients with AMD (5, 6, 7, 8). Hence, GA is, after choroidal neovascularization (CNV), the second most common cause of legal blindness due to AMD. Patients with primary GA tend to be older than those with neovascular forms of AMD at the time of initial presentation, and it has been speculated that GA occurs in eyes in which a neovascular angiogenic event has not developed. As opposed to the recent breakthrough with anti-VEGF (vascular endothelial growth factor) therapy for active neovascular AMD, there is to date no treatment available for patients with GA, other than visual aids and visual rehabilitation. Therefore, a better understanding of the pathogenesis of GA appears to be mandatory. Sensitive diagnostic tools and prognostic markers to evaluate disease stage and future progression in the individual patient are needed.

It is clinically well established that GA atrophy can affect one or both eyes (9,10). The fellow eye can be affected by any other AMD manifestation and development, including CNV or disciform scarring. It has been reported that eyes demonstrating typical early features of GA can also develop CNV; in these patients, severe and sudden visual loss occurs (11). When CNV develops in an eye with previously diagnosed pure GA, it usually has an evanescent appearance and it is often difficult to outline its borders and differentiate between hyperfluorescence resulting from the CNV and that caused by atrophic areas. In this context, careful slit-lamp biomicroscopy may allow the identification of subretinal fluid or hemorrhage, which would indicate the presence of a CNV. Optical coherence tomography (OCT) may also be helpful in identifying a CNV in these cases.


PATHOPHYSIOLOGY

Areas of GA in AMD occur at sites where macular changes at the level of the retinal pigment epithelium (RPE) and Bruch’s membrane, such as pigmentary alterations and drusen, are present (9,10,12,13). Regression of confluent, large, soft drusen may lead
to atrophy (1). Similarly, calcified deposits seem to correlate well with the development of atrophy (14). In some cases, GA occurs following the collapse and flattening of RPE detachments (1).

The pathophysiological mechanisms underlying the atrophic process are not completely understood. It is believed that lipofuscin, a by-product of incompletely digested photoreceptor outer segments that accumulates in RPE cells in atrophic AMD, plays a key role in the disease process (see also Chapters 1 and 2) (15). Histopathological studies have shown that clinical visible areas of atrophy are confined to areas of RPE and photoreceptor cell loss, and choriocapillaris closure (13,16,17). Furthermore, lipofuscin and melanolipofuscin-engorged RPE cells have been observed in the junctional zone between the atrophic and the relatively normal retina, whereas in areas of atrophy there is loss of RPE and thus of lipofuscin granules (17).

These postmortem observations suggest that lipofuscin may play a direct pathogenetic role in atrophic AMD by causing RPE cell death, with subsequent deleterious effects on photoreceptors and choriocapillaries. Alternatively, it is possible that the excessive accumulation of lipofuscin is an expression of RPE cell dysfunction and is thus the result, not the cause, of it.


IMAGING TECHNIQUES


Fundus Photography

The discrete areas of loss of RPE associated with loss of overlying photoreceptors in GA appear as areas of depigmentation on slit-lamp biomicroscopy in comparison with surrounding normal retina. The decreased retinal thickness at such sites is usually not visible on nonstereo images. Deep, large choroidal vessels may be apparent and more distinctly visible through areas of atrophic retina. Due to the low contrast, particularly in the red spectrum, the distinction of GA on fundus photographs is challenging and other imaging modalities are required to accurately identify atrophic patches.


Fluorescein Angiography

On fluorescein angiography (FA), atrophic areas are much better delineable. These appear as areas of discrete hyperfluorescence, representing a transmission defect with mild late staining. It may be difficult to differentiate between areas of atrophy and areas with fibrosis, regressed CNV, or hyperfluorescence from other causes.


Indocyanine Green Angiography

Due to atrophy of the choriocapillaris, GA appears as areas of discrete hypofluorescence with loss of the normal background signal on indocyanine green (ICG) angiography. Larger, deeper choroidal vessels are clearly visible. Compared to FA, it appears to be more difficult to distinguish between atrophic and nonatrophic retina using ICG.


Optical Coherence Tomography

Retinal thinning with loss of outer retina is observed over GA on OCT scans. Spectral-domain OCT with simultaneous confocal scanning laser ophthalmoscopy (cSLO) allows
for better 3D assessment of retinal abnormalities. Recent data suggest that OCT can reveal highly variable morphological alterations in the atrophic area and in the surrounding retina in eyes with funduscopically uniform-appearing GA (18).


Fundus Autofluorescence


Findings on Fundus Autofluorescence in Geographic Atrophy

Fundus AF findings in patients with GA are in accordance with histopathologic findings (19,20). Thus, because of the lack of RPE lipofuscin, which contains the dominant fluorophores involved in the AF signal (see Chapter 3), AF imaging shows a markedly reduced AF signal at the site of atrophic areas (Fig. 10C.1). Compared with drusen, which may also exhibit a decreased AF signal, atrophic areas typically show an even stronger reduction of AF (21). The high-contrast difference between atrophic and nonatrophic retina allows for much better delineation of atrophic areas with AF
imaging compared to conventional fundus photographs (22,23). In contrast to FA, AF imaging is a noninvasive and less time-consuming method.

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Aug 29, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Fundus Autofluorescence in Atrophic Age-Related Macular Degeneration
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