Classification of fundus autofluorescence patterns in early age-related macular disease.

PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Symmetry of bilateral lesions in geographic atrophy in patients with age-related macular degeneration.

BACKGROUND: As a cause for severe visual loss, geographic atrophy of the retinal pigment epithelium is about half as common as choroidal neovascularization in patients with advanced age-related macular degeneration. To assess symmetry, we determined intraindividual variations of various features of bilateral geographic atrophy in patients with atrophic age-related macular degeneration in a cross-sectional study. METHODS: Patients were examined with the use of a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). Digital infrared reflection images (excitation, 830 nm) and fundus autofluorescence images (excitation, 488 nm) were recorded. The eyes of each patient were compared regarding number, size, and convex hull of the atrophic areas with the use of image analysis software and with respect to fundus autofluorescence changes in the junctional zone. RESULTS: Seventy-two patients (mean +/- SD age, 76.3 +/- 7.9 years) were examined. The number of atrophic areas ranged from 1 to 23 (mean +/- SD, 4.9 +/- 4.6); the size of geographic atrophy, from 0.18 to 30.20 (mean +/- SD, 7.0 +/- 6.6) mm(2); and the size of the convex hull, from 0.18 to 39.20 (mean +/- SD, 11.7 +/- 8.4) mm(2). No statistically significant difference was found when comparing these variables between each left and right eye: number, P =.62; size, P =.81; and convex hull, P =.78. Identical patterns of fundus autofluorescence were observed in 43 (80%) of 54 patients. CONCLUSIONS: There is intraindividual symmetry in eyes with bilateral geographic atrophy in the presence of a wide range of interindividual variability. The findings are in accordance with the view that age-related macular degeneration is not merely the result of a nonspecific aging process. Symmetric manifestations, rather, reflect specific individual determinants in the pathogenesis and manifestation of the disease.

Visualization of retinal pigment epithelial cells in vivo using digital high-resolution confocal scanning laser ophthalmoscopy.

PURPOSE: To visualize retinal pigment epithelial cells in vivo by fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope. DESIGN: Experimental study and observational case report. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Digital simultaneous fluorescein and indocyanine green angiography, autofluorescence, and red-free imaging with a solid-state laser-based confocal scanning laser ophthalmoscope.

PURPOSE: To describe and to evaluate a novel confocal scanning laser ophthalmoscope (cSLO) for fluorescence angiography, fundus autofluorescence (FAF), and red-free imaging. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration.

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) has been shown to be superior to fundus photography or angiography for delineating areas of geographic atrophy (GA) in retinal pigment epithelium (RPE) and for recording variation over time. We have evaluated a method for automated computerized detection and quantitation of RPE atrophy. METHODS: AF images in vivo were recorded with a confocal scanning laser ophthalmoscope (exc. 488 nm, em. >500 nm; Heidelberg Retina Angiograph). The intensity of AF in atrophic areas was markedly decreased. Two independent readers analysed these areas in 24 right eyes manually by outlining GA areas using a mouse-driven arrow (method A) and automatically by image analysis software (Global Lab Image/2) after subjective adjustment of thresholding (method B). Agreement between observers and between methods A and B was assessed by the Bland-Altman design for method-comparison studies. RESULTS: Larger areas were measured using method A than B by both readers (agreement A/B: reader 1 mean difference 1.04 mm, 95% CI [0.66,1.42]; reader 2 mean difference 0.62 mm, 95% CI [0.43,0.81]). The agreement between the readers was mean difference 0.39 mm (95% CI [0.02,0.76]) for A and mean difference -0.03 mm (95% CI [-0.23,0.18]) for B. Features making the delineation of borders of GA difficult included large choroidal vessels with autofluorescent properties in the GA area and media opacities. CONCLUSIONS: Fundus AF cSLO imaging provides a reliable means to delineate areas of GA. The automated image analysis allows more accurate detection and quantitative documentation of atrophic areas than manual outlining. This method will be useful in longitudinal natural history studies and for monitoring effects of future therapeutic interventions to slow down GA progression in patients with advanced atrophic ARMD and other retinal diseases associated with outer retinal atrophy.

Agreement among ophthalmologists in evaluating fluorescein angiograms in patients with neovascular age-related macular degeneration for photodynamic therapy eligibility (FLAP-study).

OBJECTIVE: To determine intraobserver and interobserver variation for classifying types of choroidal neovascularizations (CNV) in exudative age-related macular degeneration (ARMD). DESIGN: Intraexaminer and interexaminer reliability study. PARTICIPANTS: Digital high-quality fluorescein angiograms of 40 patients with neovascular ARMD were evaluated independently by 16 retinal specialists. MAIN OUTCOME MEASURES: Fluorescein angiographies were presented in two randomized sequences (series A and B) to each masked reader for classification of type of CNV into classic, occult, or mixed with classic component of less or greater 50%. Agreement was evaluated by calculating kappa statistics (kappa) and intraclass correlation coefficients. RESULTS: The mean kappa coefficient was 0.64 +/- 0.11 for intraobserver variation, with a range from 0.44 to 0.89. For interobserver variation the intraclass correlation coefficients was calculated as 0.66 (95% confidence interval [CI] 0.56, 0.77) for series A and as 0.55 (95% CI 0.43, 0.67) for series B. CONCLUSIONS: Angiographic classification of CNV secondary to ARMD can vary considerably not only between observers but also for repeated evaluation by the same observer. Because various current and emerging treatments including photodynamic therapy are based on specific angiographic characteristics, accurate interpretation will become more important.