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Mihoko Suzuki, Sotaro Ooto, Christine A Curcio, Richard F Spaide; Calcified Drusen: Multimodal Clinical Imaging and Histology. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3526. doi: https://doi.org/.
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To investigate calcified drusen in patients with age-related macular degeneration with multimodal imaging and in donor eyes with histology.
Color fundus photographs, spectral-domain optical coherence tomography (OCT) and fundus autofluorescence (AF) imaging were obtained as part of a comprehensive ophthalmologic examination. Eyes with calcified drusen were identified by visualization of refractive white, glistening dots within drusen seen by color photography. Macula-wide high-resolution histological sections through the fovea and superior perifovea of short post-mortem eyes were stained with toluidine blue. Sections were examined by light microscopy. Findings from each imaging modality were catalogued.
Multimodal imaging was performed on 10 eyes. In AF imaging calcified drusen showed topographically influenced morphology. Calcified drusen in the center of macula typically showed loss of autofluorescence signal encompassed a broader area than the drusen themselves. More peripherally located neighboring calcified drusen showed autofluorescence loss in that was smaller proportionately. Peripheral to these calcified drusen were typical drusen with increased autofluorescence signal despite lacking demonstrable visible calcium, an appearance different from the autofluorescence pattern of conventional drusen. OCT demonstrated hyperreflective dots and curvilinear structures within calcified drusen, increased transmission of light surrounding the drusen in cases of geographic atrophy, and a larger overlying area of absent outer retinal bands. Of 19 calcified drusen in 6 donor eyes, all contained mineral deposits consistent with calcium. Overlying RPE was completely absent in 13, partially absent in 4, and intact in only 2. Some drusen contained Müller cell processes, RPE cells, or macrophages. Outer retinal atrophy, manifested by attenuated photoreceptor outer segments and blunted inner segments, was present overlying all calcified drusen independent of RPE status.
Calcification of drusen is considered to be a manifestation of drusen regression. There are widespread changes in the overlying retina and RPE that are larger, and can presage geographic atrophy. Calcified drusen are an important marker in the development of geographic atrophy. This study has demonstrated that multiple layers are concurrently involved, with potential impact on visual function and theories of disease pathogenesis.
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