Macular Degeneration: Fleckenstein M

Finger RP, Krohne TU, Charbel Issa P, Fleckenstein M, Scholl HP, Holz FG. · No affiliation provided · Retina. · Pubmed #19430277 No free full text.

This publication has no abstract.

Schmitz-Valckenberg S, Fleckenstein M, Scholl HP, Holz FG. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Surv Ophthalmol. · Pubmed #19171212 No free full text.

Abstract: Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression.

Finger RP, Fleckenstein M, Scholl HP, Holz FG. · Centre for International Health, Curtin University of Technology, Perth, Australien. · Pharm Unserer Zeit. · Pubmed #17957685 No free full text.

Abstract: Bei der altersabhängigen Makuladegeneration (AMD) handelt es sich um eine komplexe Erkrankung des Netzhaut-/Pigmentepithel-/ Aderhaut-Komplexes, die typischerweise zu einem Verlust der Sehschärfe und des zentralen Gesichtsfeldes führt. Bei der häufigen neovaskulären Spätform kann ein Sehverlust mittels VEGF-Inhibitoren verhindert und bei einem Teil der Patienten sogar erstmals eine Sehverbesserung erreicht werden.

Scholl HP, Fleckenstein M, Charbel Issa P, Keilhauer C, Holz FG, Weber BH. · Department of Ophthalmology, University of Bonn, Bonn, Germany. <> · Mol Vis. · Pubmed #17327825 links to  free full text

Abstract: Age-related macular degeneration (AMD) is a genetically complex disorder of the photoreceptor-RPE-Bruch's membrane-choriocapillaris complex. Family and twin studies have shown that the susceptibility for this disease is genetically influenced. The heritability has been estimated to be up to 71%. Linkage and association studies have identified several chromosomal regions that are likely to contain susceptibility loci with strongest evidence found on chromosome 1q31 and 10q26. Variants in the complement factor H (CFH) gene have been shown by several independent studies to be associated with an increased risk for AMD in Caucasian populations. These findings imply that the innate immune system may play a significant role in AMD pathogenesis. The LOC387715/HTRA1 locus within 10q26 has been identified as a second major locus contributing to AMD pathogenesis. The two late forms of AMD, choroidal neovascularization and geographic atrophy, have not been found to be different in risk allele distribution. Variants within CFH and LOC387715/HTRA1 may contribute to the increased risk of late AMD largely through their impact on precursors, such as drusen and/or other RPE/Bruch's membrane changes. Considering variants at CFH, LOC387715/HTRA1 and complement component 2-complement factor B (C2-FB), high-risk homozygotes at all three loci may have a 250-fold increased risk compared to baseline. However, the identification of genetic factors has not resulted in therapeutic strategies to modify the disease so far and additional genetic and environmental factors are yet to be discovered in order to influence the onset and the progression of AMD.

Fleckenstein M, Charbel Issa P, Helb HM, Schmitz-Valckenberg S, Scholl HP, Holz FG. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Arch Ophthalmol. · Pubmed #18852430 No free full text.

This publication has no abstract.

Schmitz-Valckenberg S, Fleckenstein M, Göbel AP, Sehmi K, Fitzke FW, Holz FG, Tufail A. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Am J Ophthalmol. · Pubmed #18514607 No free full text.

Abstract: 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.

Fleckenstein M, Charbel Issa P, Helb HM, Schmitz-Valckenberg S, Finger RP, Scholl HP, Loeffler KU, Holz FG. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Invest Ophthalmol Vis Sci. · Pubmed #18487363 No free full text.

Abstract: PURPOSE: To describe morphologic variations in outer retinal layers in eyes with atrophic age-related macular degeneration (AMD) using high-resolution, spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT scans were obtained with a combined confocal scanning laser ophthalmoscope (cSLO) and SD-OCT for simultaneous tomographic and topographic in vivo imaging. A total of 81 eyes of 56 patients (mean age, 77.8 +/- 7.4 years) with geographic atrophy (GA) were examined. Morphologic alterations were analyzed and classified in the perilesional zone, at the junction between GA and nonatrophic retina, and in the atrophic area itself. RESULTS: In the perilesional zone, distinct morphologic alterations included elevations of the outer retinal layers, thickening, and spikes of the outer hyperreflective band as well as clumps at different neurosensory retinal levels. At the junction, highly variable transitions of the outer retinal layers were present with different degrees of loss of the normal hyperreflective bands. Within the actual GA, hyperreflective clumps at different retinal levels, segmented plaques of the outer band and elevations with variable reflectivity were visualized. CONCLUSIONS: SD-OCT imaging in eyes with GA revealed a wide spectrum of morphologic alterations, both in the surrounding retinal tissue and in the atrophic area. These alterations may reflect different disease stages or, alternatively, heterogeneity on a cellular and molecular level. Longitudinal studies using in vivo SD-OCT imaging may allow evaluation of the relevance of these phenotypic changes as potential predictive markers for the progression of disease (i.e., enlargement rates of GA over time) and may be used for monitoring of future therapeutic interventions.

Finger RP, Fleckenstein M, Holz FG, Scholl HP. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Qual Life Res. · Pubmed #18365767 No free full text.

Abstract: PURPOSE: Age-related macular degeneration (AMD) has a considerable impact on older adults' independence and autonomy. Recently, patient reported outcomes (PROs) such as QoL have been met with increasing interest by the scientific community, healthcare payers and planners. Against this background, the multitude of psychometric tools used to measure QoL in AMD was reviewed. METHODS: A search of the literature from 1990 onwards yielded 355 results, out of which 58 publications were included in the review. Data regarding design, validation and extent of utilization were obtained where available. RESULTS: The National Eye Institute-Visual Function Questionnaire (NEI VFQ-25-item) was found to be the most often used (29% of studies) and best validated psychometric tool, followed by the Visual Function Questionnaire (VF-14; 17%), and the Impact of Vision Impairment Profile (IVI; 9%). Most tools that were identified have been validated for the use in AMD patients. CONCLUSION: Psychometric tools specifically designed to measure vision-related quality of life are well equipped and validated to measure QoL in AMD. More recent developments such as the Macular Disease-dependent Quality of Life (MacDQoL) questionnaire might be able to depict dimensions of vision-related QoL in greater depth. Future studies should endeavour to use a suggested standard when gathering data on vision related QoL, allowing for international comparisons.

Holz FG, Bindewald-Wittich A, Fleckenstein M, Dreyhaupt J, Scholl HP, Schmitz-Valckenberg S, Anonymous00266. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Am J Ophthalmol. · Pubmed #17239336 No free full text.

Abstract: PURPOSE: To test if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) have an impact on GA progression rates over time in atrophic age-related macular degeneration (AMD). DESIGN: Prospective longitudinal multicenter natural history study. METHODS: Standardized digital FAF images were obtained from 195 eyes of 129 patients with GA using confocal scanning laser ophthalmoscopy (excitation 488 nm, emission >500 nm). Areas of GA were quantified and patterns of abnormal FAF in the junctional zone were classified. Repeated FAF images were obtained over a median follow-up period of 1.80 years (interquartile range [IQR], 1.28 to 3.34). RESULTS: Areas of GA (median, 7.04 mm(2) at baseline; IQR, 3.12 to 10.0) showed a median enlargement of 1.52 mm(2)/year (IQR, 0.81 to 2.33). Progression rates in eyes with the banded (median 1.81 mm(2)/year) and the diffuse FAF pattern (1.77 mm(2)/year) were significantly higher compared to eyes without FAF abnormalities (0.38 mm(2)/year) and focal FAF patterns (0.81 mm(2)/year, P < .0001). Within the group of the diffuse pattern, eyes with a diffuse trickling pattern could be identified that exhibited an even higher spread rate (median 3.02 mm(2)/year) compared to the other diffuse types (1.67 mm(2)/year, P = .001). CONCLUSIONS: The results indicate that distinct phenotypic FAF patterns have an impact on disease progression in eyes with atrophic AMD and may therefore serve as prognostic determinants. The findings underscore the relevance of FAF imaging and the pathogenetic role of excessive retinal pigment epithelium (RPE) lipofuscin (LF) accumulation in GA. Natural history data and identification of high-risk characteristics will be helpful to design interventional studies aiming at slowing the spread of atrophy.