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Correlation of Lines of Increased Autofluorescence in Macular Dystrophy and Pigmented Paravenous Retinochoroidal Atrophy by Optical Coherence Tomography
Monika Fleckenstein, MD;
Peter Charbel Issa, MD;
Hans-Martin Helb, MD;
Steffen Schmitz-Valckenberg, MD;
Hendrik P. N. Scholl, MD;
Frank G. Holz, MD
Arch Ophthalmol. 2008;126(10):1461-1463.
Discrete lines of increased fundus autofluorescence (FAF) have recently been described in various retinal dystrophies.1-2 It has been shown that these lines demarcate areas with impaired retinal sensitivity from those without and may constrict or expand in different retinal dystrophies over time.1-2 Morphological changes corresponding to lines of increased FAF have not been described yet. Likewise, the mechanism underlying the abnormal accumulation of lipofuscin and increased FAF is unknown. In retinitis pigmentosa, abnormally increased FAF commonly forms a parafoveal ring or annulus. Recent optical coherence tomography (OCT) findings suggest that the band that represents the interface of the inner/outer segments of photoreceptors may be preserved within the ring.3
The imaging tool used herein (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) allows for exact correlation of simultaneously recorded confocal scanning laser ophthalmoscopy (cSLO) FAF images and high-resolution spectral-domain (SD)—OCT images. We investigated the underlying morphological SD-OCT changes in the presence of lines of increased FAF in one patient with macular dystrophy and one with pigmented paravenous retinochoroidal atrophy.
Report of Cases
Case 1
Patient 1 (Figure 1), a 47-year-old man with bilateral fundus appearance of bull's-eye maculopathy and normal scotopic and photopic full-field electroretinogram responses exhibited a ring of increased FAF that sharply demarcated a central area of severely impaired light sensitivity that had been demonstrated by fundus-controlled microperimetry.1
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Figure 1. Patient 1. Simultaneous fundus autofluorescence (FAF) and spectral domain—optical coherence tomography imaging. The line of increased FAF corresponds to a junctional zone (B and C, within black lines). RPE indicatespresumed correspondence of the retinal pigment epithelium; IPRL, interface of the inner/outer segments of photoreceptors; ELM, external limiting membrane; ONL,outer nuclear layer; OPL,outer plexiform layer; INL,inner nuclear layer; IPL,inner plexiform layer; GCL,ganglion cell layer; and RNFL,retinal nerve fiber layer.5
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Simultaneous cSLO and SD-OCT imaging revealed that the area of increased FAF corresponded to the junction between 2 different zones. Outside the ring, OCT scans showed preserved retinal layers; within the ring, the interface of the inner and outer segments of photoreceptors layer (IPRL) was absent, and the hyperreflective band that is assumed to represent the external limiting membrane (ELM) appeared to rest directly on the preserved retinal pigment epithelium (RPE) layer. The outer nuclear layer (ONL) and the more inner retinal layers appeared unaffected. Fundus autofluorescence and the RPE layer appeared normal on either side of the ring, independent of the presence of the IPRL.
Case 2
Patient 2 (Figure 2 and Figure 3), a 29-year-old man with bilateral pigmented paravenous retinochoroidal atrophy exhibited arcs of increased FAF with a crescent-like distribution surrounding the area of RPE atrophy. In the left eye, the central macula was surrounded by a ring of increased FAF that was broadened at the temporal side. Microperimetric assessment revealed the appearance of normal light sensitivity in the central macula and severely reduced light sensitivity in areas that were demarcated by the arc of increased FAF.1
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Figure 2. Patient 2; right eye. Simultaneous fundus autofluorescence (FAF) and spectral domain—optical coherence tomography imaging. The line of increased FAF corresponds with a junctional zone (B and C, within black lines). RPE indicates presumed correspondence of the retinal pigment epithelium; IPRL, interface of the inner/outer segments of photoreceptors; ELM, external limiting membrane; ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; and RNFL, retinal nerve fiber layer.5
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Simultaneous cSLO and SD-OCT imaging revealed that the line of increased FAF corresponded to the junction between a zone with preserved retinal layers on the SD-OCT scan and a zone where the presumed ELM appeared to rest directly on the RPE layer (Figure 2). In the left eye, in a broadened area with increased FAF, the IPRL was not present, but there seemed to be an increased distance between the RPE layer and the presumed ELM (Figure 3) compared with the areas with normal-appearing FAF and loss of the IPRL.
Comment
Transition zones with sharp demarcation between viable and degenerated photoreceptors and areas with direct apposition of the ELM to the RPE have been reported in histopathologic sections in a patient with retinitis pigmentosa.4 Notably, these zones also showed only minor morphological changes at the level of the RPE. The correlation of OCT bands with anatomical layers has not been totally elucidated yet; therefore, interpretation of OCT findings still re quires caution.5 However, accordance of the previous postmortem analysis with the observations of this study strongly suggest that combined cSLO-SD-OCT imaging may detect structural changes within different retinal layers in vivo that were previously only identifiable by histopathology.
The striking observation of the spatial correlation of the ring of increased FAF with the transitional zone seen by SD-OCT may add to the understanding of FAF findings. It would be conceivable that the RPE cells in the transitional zone bear an increased metabolic burden. They may be unable to phagocytize the increased demand for material and compounds from severely impaired photoreceptors. This would lead to an increased accumulation of fluorophores and, subsequently, an increased FAF signal. When photoreceptor function is finally lost, the metabolic requirements for the corresponding RPE cells are reduced. The accumulated material may be partly degraded; thus, the FAF intensities would return to normal levels.
The observation of preserved FAF in retinal areas with impaired retinal sensitivity and absence of the IPRL would suggest that normal-appearing FAF intensities do not necessarily reflect an anatomically or functionally intact photoreceptor-RPE complex. The RPE might be present despite the absence of intact photoreceptors. It may be speculated that surviving RPE cells contain lipofuscin granules that were formed prior to the occurrence of outer retinal atrophy. Because it is thought that RPE cells have no means of exocytosis of such granules, a viable RPE would continue to elicit FAF phenomena. This would also indicate that constant phagocytosis of shed photoreceptor outer segment is not required for normal FAF intensities.
AUTHOR INFORMATION
Correspondence: Dr Holz, Department of Ophthalmology, University of Bonn, Ernst-Abbe-St 2, D-53127 Bonn, Germany (frank.holz{at}ukb.uni-bonn.de).
Financial Disclosure: Dr Holz reports serving as a consultant for Heidelberg Engineering.
Funding/Support: This study was supported by grants DFG Ho 1926/1-3 from the German Research Foundation, a 2006 grant from the German Society of Ophthalmology, and grant LSHG-CT-2005-512036 from European Union framework programme 6 Integrated Project EVI-GENORET (European Vision Institute—Functional Genomics of the Retina in Health and Disease). Equipment to conduct this study was provided by Heidelberg Engineering.
REFERENCES
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1. Fleckenstein M, Charbel Issa P, Fuchs HA; et al. Discrete arcs of increased fundus autofluorescence in retinal dystrophies and functional correlate on microperimetry [published online ahead of print March 14, 2008]. Eye. doi:10.1038/eye.2008.59.
2. Robson AG, Michaelides M, Saihan Z; et al. Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence: a review and update. Doc Ophthalmol. 2008;116(2):79-89.
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3. Murakami T, Akimoto M, Ooto S; et al. Association between abnormal autofluorescence and photoreceptor disorganization in retinitis pigmentosa. Am J Ophthalmol. 2008;145(4):687-694.
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4. Flannery JG, Farber DB, Bird AC, Bok D. Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1989;30(2):191-211.
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5. Pircher M, Götzinger E, Findl O; et al. Human macula investigated in vivo with polarization-sensitive optical coherence tomography. Invest Ophthalmol Vis Sci. 2006;47(12):5487-5494.
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, and 
in panel B correspond to those in panel C.