Steffen Schmitz-Valckenberg

Evaluation of Autofluorescence Imaging with the Scanning Laser Ophthalmoscope and the Fundus Camera in Age-related Geographic Atrophy

PURPOSE To compare fundus autofluorescence images (FAF) between a modified fundus camera (mFC) and a confocal scanning laser ophthalmoscope (cSLO). DESIGN Evaluation of diagnostic technology. METHODS Thirty-two eyes of 16 patients with age-related geographic atrophy (GA) treated in an institutional setting were included. FAF images were obtained with both the cSLO (excitation, 488 nm; emission, > 500 nm) and the mFC (excitation, approximately 500 to 610 nm; emission, approximately 675 to 715 nm). Using established algorithms, images were graded by two independent observers and agreements were evaluated. The main outcome measures were image quality, quantification of total atrophy, and classification of FAF patterns. RESULTS In two eyes with advanced cataract (lens grade 7 according to the Age-Related Eye Disease Study classification), FAF image quality with both systems was not sufficient for any meaningful analysis. In the remaining 30 eyes, the mean differences of the interobserver agreements for atrophy quantification were 0.16 mm2 (95% confidence interval [CI], 0.07 to 0.38) for mFC and 0.15 mm2 (95% CI, -0.04 to 0.33) for cSLO images. Because of inferior signal-to-noise ratios, FAF pattern classification was possible in a lower number of mFC images (69%) compared with cSLO images (88%). CONCLUSIONS This study suggests that the agreements for atrophy quantification are similar with both devices. The lesser visualization of FAF patterns with the mFC and thus inferior determination of disease markers may be the result of the nonconfocality and the use of single instead of mean images compared with the cSLO. These findings may be important for the design of interventional trials as well as the routine use of FAF imaging in age-related geographic atrophy.

Real-Time In Vivo Imaging of Retinal Cell Apoptosis after Laser Exposure

PURPOSE To investigate whether the detection of apoptosing retinal cells (DARC) could detect cells undergoing apoptosis in a laser model of retinal damage. METHODS Laser lesions were placed, with the use of a frequency-doubled Nd:YAG laser, on the retina in 34 eyes of anesthetized Dark Agouti rats. Lesion size and laser-induced retinal elevation were analyzed using in vivo reflectance imaging. Development of retinal cell apoptosis was assessed using intravitreal fluorescence-labeled annexin 5 in vivo with DARC technology from baseline until 90 minutes after laser application. Histologic analysis of retinal flat mounts and cross-sections was performed. RESULTS The lateral and anteroposterior depth extension of the zone of laser damage was significantly larger for higher exposure settings. A strong diffuse signal, concentrated at the outer retina, was seen with DARC for low exposures (<300 ms and <300 mW). In comparison, higher exposures (>300 ms and >300 mW) resulted in detectable hyperfluorescent spots, mainly at the level of the inner retinal layers. Dose-dependent effects on spot density and positive correlation of spot density between lesion size (P < 0.0001) and retinal elevation (P < 0.0001) were demonstrated. Histology confirmed the presence of apoptosing retinal cells in the inner nuclear and the ganglion cell layers. CONCLUSIONS This is the first time that DARC has been used to determine apoptotic effects in the inner nuclear layer. The ability to monitor changes spatially and temporally in vivo promises to be a major advance in the real-time assessment of retinal diseases and treatment effects.

Pitfalls in Retinal OCT Imaging

Optical coherence tomography (OCT) imaging plays an important role in the management of retinal diseases. However, limitations and pitfalls should be taken into consideration when applying this noninvasive imaging technology. The aim of this review is to discuss several possible sources of error in the conduct and interpretation of OCT imaging.

Age-related macular degeneration II-Geographic atrophy

Geographic atrophy (GA) represents the atrophic late-stage manifestation of “dry” age-related macular degeneration (AMD). It is characterised by the development of atrophic patches that may initially occur in the parafoveal area [3, 13, 16, 23]. During the natural course of the disease, atrophy slowly enlarges over time, and the fovea itself is typically not involved until later (“foveal sparing”, see Fig 12.3). The pathophysiologic mechanisms underlying the disease process are not completely understood. It is thought that the accumulation of lipofuscin in the retinal pigment epithelium (RPE) cells is a by-product of incompletely digested photoreceptor outer segments and plays a key role in the disease process (see Chap. 1). Histopathologic studies have shown that clinically visible areas of atrophy are confined to areas with cell death of the RPE and collateral tissue layers, i.e. the choriocapillaris and the outer neurosensory retina [7, 14, 15]. Another important finding is the observation of lipofuscin and melanolipofuscin-filled RPE cells in the junctional zone between the atrophic and the normal retina, while areas of atrophy itself are characterised by a loss of RPE and, therefore, lipofuscin granules. Fundus autofluorescence (FAF) findings in patients with GA secondary to AMD are in accordance with these in-vitro analyses (Fig. 12.1) [10, 27]. Due to the distinct changes of the topographic distribution of RPE lipofuscin, which is the dominant fluorophore for FAF imaging (see Chap. 2), the signal is markedly reduced over atrophic areas, while high-intensity FAF levels can be observed in the junctional zone surrounding the atrophic patches. These morphological changes are usually without any correlate on fundus photography or fluorescein angiography.