13 Age-Related Macular Degeneration III — Pigment Epithelium Detachment

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13.1 Introduction

Retinal pigment epithelial detachments (PEDs) are a common feature of advanced age-related macular degeneration (AMD; Figs. 13.1a, 13.2a, 13.3a). The accumulation of fluid between Bruch’s membrane and the retinal pigment epithelial (RPE) cell monolayer is often associated with the accumulation of sub-neurosensory and intra- retinal oedema (Figs. 13.2b, 13.3b).

Over time, PEDs tend to enlarge gradually both in horizontal and vertical dimen- sions, and then flatten with the formation of subsequent subretinal fibrosis or atrophy associated with irreversible loss of neurosensory retinal function. The natural course also encompasses the development of a RPE tear, which may be associated with acute haemorrhages and additional visual loss (see Chap. 14.5) [3, 4, 6].

Detachments of the RPE from Bruch’s membrane usually occur in association with occult choroidal neovascularization spreading under the RPE cell basal membrane or by retinal angiomatous proliferation (RAP). Based on angiographic findings, so- called serous PEDs may also develop in the absence of a neovascular membrane net.

Given the constant fluid movements from the photoreceptor/RPE cell complex to the choroid, it has been speculated that barrier effects within Bruch’s membrane may contribute by deposition of lipoidal constituents to the formation of such detachments. In particular, the accumulation of neutral lipids (cholesterol esters, triglycerides, diglyc- erides, and free fatty acids) would form a hydrophobic barrier that would impair the passage of fluid and result in accumulation of fluid in the sub-pigment epithelial space.

RPE detachments would further be promoted by the mere presence of such deposits by decreasing adhesive forces between the RPE and Bruch’s membrane [1–4, 6].

13.2 FAF Findings

Fundus autofluorescence (FAF) imaging in eyes with PED secondary to AMD, idio- pathic central serous chorioretinopathy, or polypoidal choroidal vasculopathy shows

Age-Related Macular Degeneration III — Pigment Epithelium Detachment

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variable FAF phenomena [5, 7–9]. Distinct variations of the normal background FAF signal in the area of the PED can be visualised, which are not detectable using con- ventional imaging techniques such as fundus photography, fluorescein, or indocyanine green angiography.

Changes in FAF intensities in patients with PED secondary to AMD can be classi- fied into four groups. The majority of PEDs show a corresponding evenly marked and distributed increase of the FAF signal over the lesion, surrounded by a well-defined less autofluorescent halo delineating the entire border of the lesion (Figs. 13.1c, 13.2c).

It has been speculated that the ring of decreased FAF at the edge of the PED may reflect beginning organisation of the lesion or may originate from absorption effects of sub-neurosensory extracellular fluid. There are also PEDs with an intermediate (Fig.

13.3d) or a decreased FAF signal over the lesion (Fig. 13.5c), which may or may not correspond to areas of RPE atrophy or fibrovascular scaring. Rarely, a PED shows a cartwheel pattern with corresponding hyperpigmented radial lines and a diminished autofluorescence signal between those lines (Fig. 13.6c).

Of note, changes in the FAF signal in the presence of PEDs are not necessarily caused by alterations of RPE lipofuscin accumulation. Other dominant fluorophores with similar excitation and emission spectra inside the PED, such as extracellular fluid or degraded photoreceptors, may be present and contribute to typical patterns with abnormal FAF intensity. The molecular species in the sub-RPE space remain to be identified. Overall, different FAF phenotypes may reflect not only different stages in the evolution of a PED (Fig. 13.4) but also heterogeneity on a cellular and molecular level in the disease process, and may thus be relevant for future molecular genetic analyses. Future longitudinal investigations are necessary to assess whether different phenotypic patterns are of predictive significance.

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Fig. 13.1a–c Colour, fluorescein angiogram, and corresponding fundus autofluorescence (FAF) image showing a detachment of the retinal pigment epithelium due to age-related macular degeneration with increased FAF signal over the lesion and a surrounding area of decreased autofluorescence. Note the notch indicating occult choroidal neovascularisation in the fluorescein angiogram

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Chapter 13 Age-Related Macular Degeneration III—Pigment Epithelium Detachment 169

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Fig. 13.2a–c Colour, optical coherence tomography, and corresponding fundus autofluorescence (FAF) image of a further detachment of the retinal pigment epithelium with increased FAF intensity over the lesion (possible RAP lesion)

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Fig 13.4 Variation of fundus autofluorescence (FAF) signal in the presence of a detachment of the retinal pigment epithelium over time. a Corresponding in- creased FAF and dark halo at baseline. b After 6 months, the autofluorescence signal decreases in the area of the detachment while the border becomes bright- ly autofluorescent

Fig. 13.3a–d Colour, optical coherence tomography, fluorescein angiogram, and corresponding fundus autofluorescence (FAF) image showing a large detachment of the retinal pigment epithelium with intermediate FAF signal and a surrounding halo of decreased autofluorescence signal in the presence of a RAP lesion

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Fig. 13.5a–c Colour, indocyanine green angiogram, and corresponding fundus autofluorescence (FAF) image showing a detachment of the retinal pigment epithelium due to age-related macular degeneration, with decreased FAF signal over the lesion. Note the choroidal neovascular membrane at the inferior nasal part of the lesion

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Fig. 13 6a–c Colour, fluorescein angiogram, and corresponding fundus autofluorescence (FAF) image of a detachment of the retinal pigment epithelium, showing a cartwheel pattern with corresponding hyperpigmented lines and diminished FAF signal between those lines

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