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Almut Bindewald,
Alan C Bird,
Samantha S Dandekar,
Joanna Dolar-Szczasny,
Jens Dreyhaupt,
Frederick W Fitzke,
Wilma Einbock,
Frank G Holz,
Jork J Jorzik,
Claudia Keilhauer,
Noemi Lois,
Juliane Mlynski,
Daniel Pauleikhoff,
Giovanni Staurenghi,
Sebastian Wolf
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ABSTRACT: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD).
FAF images were recorded in eyes with early AMD by confocal scanning laser ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and emission above 500 or 521 nm (barrier filter). A standardized protocol for image acquisition and generation of mean images after automated alignment was applied, and routine fundus photographs were obtained. FAF images were classified by two independent observers. The kappa statistic was applied to assess intra- and interobserver variability.
Alterations in FAF were classified into eight phenotypic patterns including normal, minimal change, focal increased, patchy, linear, lacelike, reticular, and speckled. Areas with abnormal increased or decreased FAF signals may or may not have corresponded to funduscopically visible alterations. For intraobserver variability, kappa of observer I was 0.80 (95% confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84). For interobserver variability, kappa was 0.77 (95% CI, 0.67-0.87).
Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast to a nonspecific aging process. The results indicate that the classification system yields a relatively high degree of intra- and interobserver agreement. It may be applicable for determination of novel prognostic determinants in longitudinal natural history studies, for identification of genetic risk factors, and for monitoring of future therapeutic interventions to slow the progression of early AMD.
Investigative Ophthalmology & Visual Science 10/2005; 46(9):3309-14. · 3.60 Impact Factor
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ABSTRACT: To describe and to evaluate a novel confocal scanning laser ophthalmoscope (cSLO) for fluorescence angiography, fundus autofluorescence (FAF), and red-free imaging.
Digital infrared, red-free, FAF, fluorescein, and indocyanine green (ICG) angiography images were obtained with a cSLO in 766 patients. An optically pumped solid-state laser generates the excitation wavelength (488 nm) required for red-free, FAF, and fluorescein angiography images. For ICG angiography and infrared imaging, diode laser sources at 790 and 820 nm are used. Further features include an internal fixation control and a focus range of -24 to +30 diopters.
High-image quality is achieved with a resolution of up to 5 microm per pixel in 30- x 30-degree images and allows for accurate delineation of normal and pathologic features. Simultaneous angiography offers high-contrast images. Corresponding display of quasi-simultaneous frames facilitates interpretation. A small focus difference between fluorescein and ICG scans occurs because of chromatic aberrations. Automated alignment and generation of mean images from several single frames allow for acquisition of high-resolution FAF images.
Various laser-source related, optical, and electronic innovations improve cSLO fundus imaging for routine clinical application. A solid-state laser has advantages compared to argon gas laser sources, including less space occupation, heat emission, and noise production.
Retina 07/2005; 25(4):405-16. · 2.81 Impact Factor
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ABSTRACT: To present application of a confocal Scanning Laser Ophthalmoscope (cSLO) for fundus autofluorescence examination, as a new method of visualization of retinal pigment epithelium and its possible significance in the diagnosis of different retinal diseases.
Typical autofluorescence images in age-related macular degeneration (AMD), Stargardt disease, Best disease and pattern dystrophies are presented, based on the own experience and literature data. Autofluorescence images were obtained with a cSLO using an argon laser for generation of excitation light at 488 nm and a barrier filter >500 nm for the detection of the emitted signals.
A variety of autofluorescence patterns, associated with the accumulation of lipofuscin in RPE cells, was found in the above entities.
Presented method of fundus autofluorescence examination gives new possibilities in studying the pathogenetic mechanisms in various retinal diseases and may be useful in monitoring the follow-up and the effects of the treatment.
Klinika oczna 02/2005; 107(7-9):544-7.
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ABSTRACT: To investigate retinal sensitivity in the junctional zone of geographic atrophy (GA), with variations in fundus autofluorescence (FAF) in patients with advanced age-related macular degeneration (AMD).
The spatial distribution and intensity of FAF were recorded with a confocal scanning laser ophthalmoscope (SLO). Eyes had normal background FAF (group 1) or increased FAF (group 2) surrounding the atrophic patches. Retinal sensitivity was assessed by applying light stimuli with static automated full-threshold fundus perimetry with a modified SLO. Threshold sensitivities were compared with age-matched normal sensitivities.
Thirty-nine eyes of 39 patients with GA were included. Group 2 had a higher percentage of all test points outside the GA area, with decreased retinal sensitivity (44.9% +/- 28.7%) compared with group 1 (20.7% +/- 12.7%; P = 0.0063; multiple regression model; outcome variable is retinal sensitivity; covariates are group affiliation and GA area). Within group 2, the average percentage of stimuli in areas of normal FAF with reduced sensitivity was 38.0% +/- 33.0%, whereas the average percentage of stimuli in areas of elevated FAF with reduced sensitivity was 52.6% +/- 29.7% (P = 0.023, Wilcoxon signed rank test).
Areas of increased FAF outside GA may be associated with variable degrees of loss of retinal sensitivity and suggest a functional correlate of excessive accumulation of retinal pigment epithelium lipofuscin in AMD. Combining in vivo recording of FAF and retinal sensitivity, using SLO technology, may give important clues in the understanding of mechanisms of disease.
Investigative Ophthalmology & Visual Science 01/2005; 45(12):4470-6. · 3.60 Impact Factor
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ABSTRACT: To review current knowledge of key pathogenetic pathways in age-related macular disease (AMD).
Experimental evidence and clinical observations are reviewed.
A number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment of lysosomal functions, deposition of subsequently incompletely degraded material at the basal RPE cell side and alterations in Bruch's membrane extracellular matrix, immunologic responses to extracellular material (drusen) with subsequent growth of drusen, induction of choroidal neovascularization as a result of imbalance between anti-angiogenetic and proangiogenetic factors as well as cell death (geographic atrophy) without prior neovascular events.
Understanding is expanding regarding the sequence of events that lead to early and late lesions in AMD. Therapeutic approaches that focus on the molecular mechanisms are more likely to succeed than currently available treatment options as exemplified by the management of choroidal neovascularisations.
Albrecht von Graæes Archiv für Ophthalmologie 09/2004; 242(8):710-6. · 2.17 Impact Factor
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ABSTRACT: To visualize retinal pigment epithelial cells in vivo by fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope.
Experimental study and observational case report.
Digital in vivo autofluorescence images were recorded with a confocal scanning laser ophthalmoscope (excitation, 488 nm; emission, >500 nm) and compared with confocal scanning laser ophthalmoscope and fluorescence microscopic recordings from human donor eyes.
A uniform pattern of the polygonal retinal pigment epithelial cell layer was visualized in vivo outside of absorbing retinal vessels and macular pigment. Autofluorescence intensities of individual cells showed marked variation. The pattern corresponded to in vitro findings. Visualization is based on the topographic distribution of autofluorescent lipofuscin granules and melanin granules in apical retinal pigment epithelium cytoplasm.
High-resolution autofluorescence imaging may be useful to determine morphologic and lipofuscin-dependent alterations in retinal diseases and may be applicable for monitoring effects of therapeutic interventions targeting the retinal pigment epithelium.
American Journal of Ophthalmology 03/2004; 137(3):556-8. · 4.22 Impact Factor
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ABSTRACT: Ophthalmic imaging technology has revolutionized fundus examination. FAF imaging represents one of various novel tools and
provides information over and above fundus photography, fluorescence angiography and optical coherence tomography. This noninvasive
diagnostic tool visualizes age- and disease-related metabolic changes of the retinal pigment epithelium. The autofluorescence
signal mainly derives from dominant fluorophores in lipofuscin granules of the RPE. Lipofuscin accumulation represents a common
downstream pathogenetic pathway in many retinal and macular disease entities.Thus FAF imaging contributes significantly to
our understanding of the pathophysiology and treatment of various retinal diseases.
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