Ординатура / Офтальмология / Английские материалы / Atlas of Fundus Autofluorescence Imaging_Holz, Schmitz-Valckenberg, Spaide, Bird_2007

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Fig. 9.17  Bietti crystalline corneoretinal dystrophy. Fundus photographs, fundus autofluorescence (FAF) image, blue-light reflectance image, and fluorescein angiogram of a 25-year-old woman. The autofluorescence background signal is severely reduced. Furthermore, reticular-like structures with increased intensity can be observed that do not seem to be related to any other structures seen on the other imaging modalities

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Fig. 9.18  X-linked retinoschisis. Top row: Fundus autofluorescence (FAF) images of a 35-year-old man with retinoschisis. FAF imaging showed levels of increased and decreased intensity in the central macula due to compression of the neural elements containing luteal pigment. Note part of an oval ring at the inferior retina of the right eye, corresponding to clinically visible retinoschisis. Middle and bottom row: Fundus photographs, horizontal OCT scans and FAF images of another patient with X-linked retinoschisis showing a similar FAF phenotype

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Fig. 9.19  Choroideremia. This 42 year old male with a long history of choroideremia had visual acuities of 6/6 in the right and 6/9 in the left eye. Fundus autofluorescence imaging (middle row) reveals a severly reduced background signal and visualizsation of underlying choroidal vessels. The preserved island in the central retina can be easily identified and corresponds to flourescein angio­ graphy findings (bottom row). Note that the fundus photography (top row) and fluorescein angiography were performed two years before FAF imaging

Forms of Retinal Dystrophies

Monika Fleckenstein, Hendrik P.N. Scholl, Frank G. Holz

10.1 Introduction

Discrete, well-defined lines of increased fundus autofluorescence (FAF) may occur in various forms of retinal dystrophies [1–12]. These lines usually have no visible correlate on fundus biomicroscopy or fluorescein angiography and are thought to originate from excessive fluorophore (e.g. in lipofuscin granules) accumulation at the level of the retinal pigment epithelium (RPE) cell monolayer. There is evidence from combined functional investigations that these lines reflect the border of impaired retinal sensitivity [2–4, 8–10]. Despite the variable orientation of this line in different enti- ties—such as orientation along the retinal veins in pigmented paravenous chorioretinal atrophy (PPCRA) or a ring structure in retinitis pigmentosa (RP) or cone-rod dystrophy (CRD)—the similar appearance on FAF images and the concordance of functional findings indicate that these lines in heterogeneous diseases entities share a common underlying pathophysiologic mechanism.

10.2

Different Orientation of Lines of Increased FAF

10.2.1

Orientation Along Retinal Veins

Orientation of such a line along retinal veins can be observed in patients diagnosed with PPCRA (Figs. 10.1a). The phenomenon of orientation of the progressive atrophy of deep retinal layers including the RPE and the choriocapillaris along anteriorly located larger retinal venous vessels is obscure. It may be speculated that the topographic distribution of the deep changes results from a release of cytokines from vascular cellular elements, and thus “communication” with anatomic levels beneath the inner retina may play a role. It is remarkable that the orientation of the line of increased

122 Monika Fleckenstei, H.P.N. Scholl, Frank G. Holz

FAF along the retinal veins of eyes at more advanced stages of PPCRA (Fig. 10.1a, left eye) finally appears to result in the formation of a ring-like structure in the parafoveal region. This finding may also indicate a related pathomechanism leading to formation and constriction of the parafoveal ring in RP.

10.2.2 Ring Shape

A line of increased FAF in the form of a parafoveal ring of variable eccentricity has been described in patients with RP [1–4, 8–11] (Fig. 10.2a), Leber’s congenital amaurosis (LCA) [5], CRD [6, 7, 9, 11], and X-linked retinoschisis (XLRS) [12].

A ring of increased FAF can be detected in some patients with RP and normal visual acuity and has been demonstrated to surround areas of normal FAF. In some patients, the ring has been shown to constrict progressively over time [10]. It is still unknown why such a ring is not found in all patients with RP who demonstrate clinical evidence of macular sparing. Two LCA patients exhibiting a ring of increased FAF have recently been described [5]. Despite severe visual impairment, the ring is surrounded by almost normal FAF. By contrast, in the reports on a ring of increased FAF in CRD [6, 7, 9, 11], and XLRS [12], respectively, the ring has been reported to encircle areas of reduced or absent FAF, corresponding to macular atrophy.

10.3

Functional Correlate of Lines/Rings of Increased FAF

Functional analyses of the line/ring of increased FAF have been performed in RP [3, 4, 8–10] and CRD [9].

In RP it has been demonstrated that patients with larger FAF rings also had larger central visual fields [3, 4, 8, 10]. Furthermore, Robson and colleagues first showed a high correlation between the pattern electroretinogram (ERG) P50 amplitude— a valuable indicator of macular function—and the size of the abnormal ring [3]. Using fine matrix mapping, they could further demonstrate that photopic sensitivity was preserved over central macular areas, but there was a gradient of sensitivity loss over high-density segments of the ring and severe threshold elevation outside the arc of the ring. Scotopic sensitivity losses were more severe, and they encroached on areas within the ring [4].

Popovic and co-workers confirmed by fundus perimetry that retinal sensitivity was preserved within the ring and was lost outside the ring regardless of whether the FAF pattern was normal or whether atrophic lesions of the RPE were already present or not [8]. (Fig. 10.2c shows the fundus perimetry in a patient with autosomal-dominant RP.)

It has been concluded that the ring of increased FAF in RP demarcates areas of preserved central photopic function and that constriction of the ring may mirror progressive visual field loss by advancing dysfunction that encroaches over areas of central macula [3, 4, 10].

There are few reports about rings of increased FAF in CRD [6, 7, 9]. In the majority of these patients, the ring encircles areas of central atrophy (Fig. 10.3a). Functional assessment has been performed in only a few patients with CRD [9]: Robson et al. could demonstrate that the pattern ERG P50 amplitude was inversely related to the size of the FAF ring; by fine-matrix mapping they revealed a gradient of sensitivity loss across the arc of increased FAF.

In a patient with macular dystrophy (Fig. 10.3), who displayed a ring of increased FAF that surrounded areas of decreased/absent FAF, fundus perimetry revealed (Figs. 10.3c) that within the ring, independent of a normal or abnormal FAF signal, there was light sensitivity loss. Outside the ring, the FAF signal and light sensitivity were almost normal. These findings were exactly opposite to the findings in RP where the central sensitivity was preserved (Fig. 10.2c).

Despite a different orientation of the line in PPCRA, fundus perimetry has revealed that the area with impaired sensitivity exceeded the area of RPE cell loss and was precisely delineated (Figs. 10.1c). In the central retina and in the periphery that was not framed by the line, the FAF signal was normal, and light sensitivity was preserved. Within the area outlined by increased FAF, independently of a normal or abnormal FAF signal, there was impaired light sensitivity. These observations are in accordance with the findings in RP whereby the ring or line of increased FAF represented the border between functional and dysfunctional light sensitivity.

At this interface, there may be a higher phagocytic and, thus, metabolic load of the corresponding RPE cells, with subsequent excessive accumulation of fluorophores in the lysosomal compartment resulting in a line of increased signal that can be visualized by FAF imaging. It is remarkable that the FAF signal on both sides of this demarcation line in most of these cases was normal or near normal (Figs. 10.1a, 10.2a, 10.3a), although on one side, there was impaired sensitivity.

Robson and colleagues suggested that restoration of normal FAF intensity over concentric areas outside the ring in RP may indicate continued but possibly impaired phagocytosis and removal of abnormal material, or that it could be explained by loss of photoreceptor cells [3, 4, 10]. Scholl et al. concluded that normal or near-normal FAF may be present in areas of photoreceptor dysfunction and that a normal FAF reflects the presence of structurally intact photoreceptors and the integrity of the photo­ receptor/RPE complex rather than normal photoreceptor function [5].

In the few histopathological reports from eyes with RP, it has been noted that des­ pite obvious photoreceptor degeneration, the RPE may display only minor morphological abnormalities. It was hypothesised that there is a high capacity of the “young” RPE to compensate for excessive photoreceptor cell degeneration before the RPE cell layer eventually suffers collateral damage and, finally, cell death [13].