The visibility of retinal amyloid deposits as a biomarker of Alzheimer’s disease when imaged in polarized light through the cornea

Abstract

AbstractBackgroundWe previously reported a novel, dye‐free method to image amyloid deposits in the retina. Using polarized light interactions to create deposit contrast, the number of deposits in ex vivo retinas predicted the severity of brain amyloid found in association with Alzheimer’s disease (AD). Here we describe the effect of the potential range of corneal interactions with polarized light on the visibility of these retinal deposits when imaged in vivo.Method52 retinal amyloid deposits, positive for thioflavin (Fig 1) and with a range of visibility in polarized light were imaged ex vivo in retinas of 12 participants with a moderate (2) or high (10) likelihood of Alzheimer’s disease, based on brain pathology. New images of each deposit were created by combining the polarized light interactions of the deposit and surrounding retina with the known range of interactions of human corneas with polarized light. The varying contrasts of each deposit with 45 different sets of corneal properties (a total of 2340 deposit images) were compared to the initial ex vivo images.ResultAs a function of the modelled corneal properties, the root mean square (RMS) contrast of each deposit both increased and decreased from that without a cornea (Fig 2). On average, RMS contrast across deposits combined with a cornea decreased 12% from that without a cornea. For 3% of deposit images, there was a corneal property that reduced the deposit contrast by over 50% (Fig 2). However, even in these cases, because of the variation in interaction with polarized light across the deposit (Fig 3), the deposit remained visible against the background retina.ConclusionAlthough the cornea interaction with polarized light will affect images of amyloid deposits in the retina taken with our non‐invasive method, all cases investigated are predicted to remain visible against the background retina. In addition, during in vivo imaging, an established method of compensating for an individual’s corneal interaction with polarized light, would guarantee 100% visibility. Thus, in vivo, our retinal imaging method is predicted to give a biomarker of the severity of amyloid in the brain found in association with Alzheimer’s disease.