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Laura Emptage, Marsha L Kisilak, Matthew Wilson, Zoya Leonenko, Melanie C W Campbell; Sensitivity and Specificity of Fluorescence and Polarimetry of the Retina in Alzheimer’s Disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3366.
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Here we investigate the sensitivity and specificity of fluorescence in the detection of amyloid β in human retinas of patients with Alzheimer’s disease (AD). Amyloid β is over expressed in the diseased brain, resulting in a neurotoxic effect. It is an accepted marker of disease, used for diagnosis post-mortem, so its presence in the retina presents an opportunity for a noninvasive diagnostic. We investigated visibility of amyloid β deposits using polarimetry in diseased and non-diseased retinas.
: Ocular tissues were provided by the Eye Bank of Ontario. Ex vivo retinas were stained with thioflavin S and flat mounted from eyes of those with a diagnosis of AD (n=19) and those with no history of AD (n=18) and excluded those with a diagnosis of glaucoma. Retinas were examined using fluorescence in both transmission and confocal scanning microscopy for amyloid β deposits. A subset of the retinas was examined for polarization properties using a polarimeter on a fluorescence microscope. In diseased retinas (defined by an AD diagnosis and positive fluorescence), we counted the number of fluorescing deposits that also had polarization contrast. In non-diseased retinas we counted the number of locations showing polarization contrast.
Of those retinas that were positive for thioflavin S staining of amyloid β, 72.6% of subjects had a positive AD history (positive predictive value), and of retinas that tested negative, 81.3% of subjects did not have an AD history (negative predictive value). A lower positive predictive value may arise from incomplete medical histories or undiagnosed disease. The negative predictive value may be lower due to the challenging differential diagnoses of dementia. When examined with polarimetry, a generator position giving circularly polarized light and an analyzer sampling the orthogonal circular polarization produced visibility of deposits in 77.4% of locations in diseased retinas with positive fluorescence. 22.6% of retinal locations, positive in polarimetry were false negatives.
Thioflavin S staining in the retina shows an 84.2% sensitivity and 72.2% specificity in detecting AD. The use of crossed circular polarization showed a high specificity to amyloid β deposits but produced some false negatives. This method shows promise for the imaging of amyloid β in the retina of the living eye as a marker of Alzheimer’s disease.
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