Macular Degeneration: Bindewald-Wittich A

Holz FG, Helb HM, Bindewald-Wittich A, Scholl HP. · Universitäts-Augenklinik, Bonn. · Internist (Berl). · Pubmed #16341677 No free full text.

Abstract: Age-related macular degeneration (AMD) is now the most common cause for blind registration in all developed countries. Epidemiologic data indicate that there are 4.5 millions affected in Germany with constant increase in incidence and prevalence with subsequent considerable health economic implications. Late manifestations of the disease result in the inability to read and to perform daily tasks. Therefore, there is an urgent need for efficacious prophylactic and therapeutic measures to prevent irreversible loss of central vision. Based on a better understanding of the underlying molecular mechanisms new therapeutic approaches have been brought forward and expand previous approaches such as thermal laser surgery or photodynamic therapy. Repeated intravitreal injection of anti-VEGF (vascular endothelial growth factor) agents as well as corticosteroids have a beneficial effect on growth and permeability of neovascular membranes. The risk for progression from early to late stages of AMD can be reduced with certain antioxidative preparations (AREDS medication) in presence of defined funduscopic signs. Early diagnosis is key for all currently available interventions since a beneficial effect can only be achieved in early stages of the disease process.

Han M, Giese G, Schmitz-Valckenberg S, Bindewald-Wittich A, Holz FG, Yu J, Bille JF, Niemz MH. · University of Heidelberg, Mannheim Biomedical Engineering Laboratories, Faculty of Clinical Medicine, Heidelberg, Germany. · J Biomed Opt. · Pubmed #17477727 No free full text.

Abstract: The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

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.

Schmitz-Valckenberg S, Bindewald-Wittich A, Dolar-Szczasny J, Dreyhaupt J, Wolf S, Scholl HP, Holz FG, Anonymous00317. · Department of Ophthalmology, University of Bonn, Bonn, Germany, and First Eye Hospital, University of Lublin, Poland. · Invest Ophthalmol Vis Sci. · Pubmed #16723482 links to  free full text

Abstract: PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.