Macular Degeneration: Keilhauer C

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.

Bindewald A, Bird AC, Dandekar SS, Dolar-Szczasny J, Dreyhaupt J, Fitzke FW, Einbock W, Holz FG, Jorzik JJ, Keilhauer C, Lois N, Mlynski J, Pauleikhoff D, Staurenghi G, Wolf S. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, 53127 Bonn, Germany. · Invest Ophthalmol Vis Sci. · Pubmed #16123434 links to  free full text

Abstract: 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.

Bindewald A, Schmitz-Valckenberg S, Jorzik JJ, Dolar-Szczasny J, Sieber H, Keilhauer C, Weinberger AW, Dithmar S, Pauleikhoff D, Mansmann U, Wolf S, Holz FG. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany. · Br J Ophthalmol. · Pubmed #15965170 links to  free full text

Abstract: AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.