Role of macular pigment density in the pathophysiology, clinical outcome and therapy of age-related maculopathy

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In the industrialised world age-related macular degeneration (AMD) is the leading cause for legal blindness beyond the age of 50 years. Recent studies indicate that the macular pigment (MP) density may play a central role in the development and progression of the disease. It has been demonstrated that the MP density can be increased by dietary supplementation. Our long-term goal is to identify the role of macular pigment in the pathogenesis and therapy of AMD. This is not only to improve understanding about the impact of macular pigment density on age-related maculopathy (ARM) and AMD but also to find an approach to enhance macular pigment density in terms of therapeutic intervention. First results of MP density measurements with a modified confocal laser scanning ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany) show that this method allows the quantification of the MP density in a clinical setting. We will evaluate the method by testing its reproducibility, correctness, and the influence of external/internal factors on the measurements. 10 healthy subjects will be examined at 4 different dates and twice within one hour at each examination date. We will also optimise the mode of analysis and compare the results to those obtained with an alternative objective biochemical method (HPLC). For HPLC analysis we will include retinas from five human donor eyes in the study. Subsequently we will establish reference values for a normal population and compare these to the MP density values obtained from ARM-patients in a cross-sectional study. The persons recruited for defining reference should be subjects without retinal pathology; a number of 20 for each decade between the age of 30 and the age of 80 years will be examined. Additionally we will examine patients with ARM and early atrophic AMD in a cross sectional study in order to achieve a good profile of MP density values in ARM and AMD patients. We will include unilateral and bilateral early disease or the second eye in patients with unilateral end-stage AMD. In comparison to the reference values it could be possible to draw conclusions about the relation of ARM and AMD on one hand and MP density on the other. This will improve the interpretation of MP values obtained from ARM patients, help to identify patients with low MP density, and probably improve the early diagnosis of patients at high risk for developing AMD. These tasks will be performed within the first two years of the project. In the last quarter of this period we will elaborate a study protocol for a prospective randomised multi-center study on the macular pigment density under dietary supplementation of lutein and/or zeaxanthin, which is planned for the following two years. Simultaneously, we will make this method available for all other clinical studies within the DFG-priority program AMD. Specifically, we will collaborate with Prof. Dr. H. Hense (University of Muenster) who is interested in using this method in the prospective study to identify prognostic factors for the progression of ARM. In summary, these studies will improve understanding of MP in AMD and open a perspective for therapeutic interventions in the pathologic mechanisms.