Search

Background: We 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. Method: 52 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. Result: As 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. Conclusion: Although 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. [ABSTRACT FROM AUTHOR]

Background: In humans and the naturally occurring canine model of Alzheimer's disease (AD), we and others observe amyloid deposits in the retina en face. We have previously shown that detecting the number of amyloid deposits with polarised light, using wide field, dye free retinal imaging, can predict the degree of severity of AD pathology in the brain. But some who take thin, transverse retinal sections find amyloid while others do not. Here, we report the surface area of retinal amyloid deposits in human and the canine model of AD. Method: Formalin‐fixed retinas from 29 individuals with a moderate to high likelihood of AD (with some comorbidities excluded) and 20 canines were flat‐mounted and imaged in florescence and polarized light (Fig 1). The full retina was imaged for 24 human and 16 canine retinas. For 4 canines, in‐vivo blue light fluorescent retinal images were collected before and after injection of an amyloid dye, CRANAD‐28. Deposits visible only after injection were counted. Fluorescence and polarization images were compared post‐mortem in a canine after an injection of CRANAD‐28. Amyloid deposits were segmented using custom methods. The total area of segmented deposits was then divided by the total retinal area imaged. Result: In retinas from individuals with AD brain pathology, the area of the retinal covered by amyloid deposits was on average 0.01% and correlated with the number of deposits (Fig 2). In vivo (Fig 3), the area of the canine retina covered by amyloid deposits was on average 0.29% (Fig 4). In one ex vivo retina, fluorescent and polarization positive deposits had a concurrence of 93% and the average area of fluorescent deposits (0.14%) was larger than the same deposits imaged in polarimetry (0.08%) (Fig. 5). Conclusion: These findings and our previous report of an almost constant density of amyloid deposits across the retina, should guide in vivo imaging of amyloid in the retina as a biomarker of AD. Across all human and canine retinas, amyloid deposits covered less than 0.6% of the retinal surface. Careful, extensive sampling is needed. The surface area of amyloid deposits is an additional potential biomarker of disease severity. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) is a vascular brain disease with risk of severe complications, and high prevalence in those with Alzheimer's disease (AD). Characteristic amyloid beta deposits in blood vessels in the cerebrum are challenging to diagnose. Amyloid deposits in blood vessels in human retinas have been previously reported. Here, we characterize postmortem, retinal amyloid angiopathy (RAA) in individuals with AD and/or CAA brain pathology. We propose a staging of RAA which could be extended to in vivo imaging, modified from CAA staging in the brain. Method: Correlation of severity of brain pathology for AD and CAA was assessed for 52 individuals. Formalin fixed retinas from 6 of these individuals were whole‐mounted and stained with thioflavin S and DAPI, then imaged in polarized light and confocal microscopy with 3 florescence channels. While following blood vessels systematically, images of RAA were collected. Result: Brain pathology due to CAA increased in severity with increasing severity of AD pathology as previously reported (Figure 1). RAA was present in all donors with evidence of brain CAA and in two donors with no evidence of brain CAA (Figure 2). Amyloid present in vessels can be imaged dye‐free in polarized light. Our proposed staging of RAA severity is modified from two used in the brain (Figures 3‐6). Stage 1): Amyloid within the vessel and not filling the lumen of the vessel: 1A) Amyloid is not circumferential; 1B) Amyloid is circumferential. Stage 2): Amyloid completely fills the lumen of the vessel. Stage 3): Amyloid both within and touching the outside of the vessel, analogous to dysphoric CAA. Conclusion: Amyloid angiopathy in the retina (RAA) may occur concurrently with and potentially prior to brain CAA. Further, severity of RAA could be monitored through the proposed staging which in turn could allow comparison of severities of CAA and RAA. This would elucidate whether RAA severity is a good predictor of CAA severity. Our data confirm the previously reported correlation between brain CAA and AD. Further development of RAA imaging in the living eye may allow earlier and improved diagnosis of brain CAA, facilitating the development and testing of new treatments. [ABSTRACT FROM AUTHOR]

In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) and age‐related macular degeneration (AMD), both associated with ageing, share common underlying pathology, in that both have been shown to be associated with retinal amyloid deposits. However, amyloid in association with AD has been found in more anterior retinal layers, while amyloid in AMD is typically found in association with drusen, in posterior retinal layers. Here, we compare amyloid deposits found in anterior and posterior layers of the retina. Method: Eyes were obtained from donors, including those with an intermediate (n=2) or high likelihood of AD (n=10). The severity of AD was assessed from brain pathology. Retinas were stained with 0.1% Thioflavin‐S, counter‐stained with DAPI and flat mounted. Retinal deposits were imaged using a fluorescence microscope fitted with a polarimeter. For each deposit, retinal layer was recorded (anterior, n=264; posterior, n=65). From 16 polarimetric images, interactions with polarized light were derived and image texture was assessed via multifractal analysis (MFA). 15 MFA properties were calculated. Using principal component analysis, the polarimetric and MFA variables which explain most of the variance within each group of deposits (anterior and posterior) were determined. These variables were then input into a non‐parametric discriminatory analysis to separate and classify deposits by retinal location (anterior or posterior). Result: Following principal component analysis, 12 polarimetric and 7 MFA properties were retained. Using the 5 nearest neighbours, a non‐parametric discriminate analysis was able to discriminate between deposits found in the anterior and posterior of the retina with success rate of 76% (+/‐3%) using 4‐fold cross‐validation. Conclusion: In conclusion, a combination of polarimetric properties and textural features of retinal amyloid deposits can be used to discriminate between anterior and posterior deposits. This suggests that the properties of deposits found in AD (expected in anterior layers) and AMD (expected in posterior layers) can be differentiated. Furthermore, an ability to distinguish these two types of retinal amyloid deposits in live‐eye imaging would assist their differential classification as associated with AD or AMD pathology. This could improve specificity of diagnosis in each of these conditions. [ABSTRACT FROM AUTHOR]

In the following point-counterpoint article, internationally-acclaimed myopia researchers were challenged to defend the two opposing sides of the topic defined by the title; their contributions, which appear in the order Point followed by Counterpoint, were peer-reviewed by both the editorial team and an external reviewer. Independently of the invited authors, the named member of the editorial team provided an Introduction and Summary, both of which were reviewed by the other members of the editorial team. By their nature, views expressed in each section of the Point-Counterpoint article are those of the author concerned and may not reflect the views of all of the authors. [ABSTRACT FROM AUTHOR]

The degree of polarization (DOP) of the light reflected from the optic nerve head has been assessed by means of a polarimetric scanning laser ophthalmoscope as a function of the age of the participants. Four fundus images corresponding to independent polarization states in the recording pathway were used to compute the spatially-resolved DOP. This was not uniform across the optic nerve head and depended on both the location and the participant’s age. Along a peripapillary annulus the DOP followed a double-peak pattern. Moreover, the values along this annulus decreased significantly with increasing age. This depolarization appears to originate in part in the retinal nerve fiber layer. Detailed age-dependent knowledge of the ocular depolarization properties may help to improve clinical diagnosis of the retinal nerve fiber layer. [ABSTRACT FROM AUTHOR]

Abstract We have studied the spatially resolved polarization properties of the in vitro intact old human crystalline lens (from 56 to 88 years old) by using Mueller-matrix imaging polarimetry. Analysis was performed within an average of 54 h of death. Results show that the overall retardation is small (7° on average) and decreases from the centre of the lens to the periphery. Lenticular birefringence is linear but has a spatial dependence, reducing outwards along the radius. The distribution of azimuthal angle of the birefringent structure of the crystalline lens changes depending on each individual lens. Diattenuation and polarizance were found to be small, however, depolarization was about 35% for the set of lenses studied here. [ABSTRACT FROM AUTHOR]

Photorefractive methods allow rapid measures of the refractive and accommodative state of infants and young children whose brief attention and co-operation limit the use of more traditional methods such as retinoscopy and autorefraction. Three methods have been defined: orthogonal, isotropic and eccentric. We provide a common geometrical optical analysis For these three methods where the photorefractive pattern is defined at the plane of focus of the camera. Since this plane is conjugate with the detector plane of the camera then the critical optical parameters can be defined without reference to the design of the camera by simply determining the relative magnification of the projected image of an object photographed at the cameras plane of locus. Specifically the pattern width CF (mm) over a photorefractor's working range can be defined for the isotropic and orthogonal methods as: [This Eqe. can not be change in ASCII code] and for the eccentric method as: [This Eqe. can not be change in ASCII code] where K is a myopic refractive error of the eye (dioptres) (K < 0) P the distance of the flash source to the eye (dioptres) L the distance in front of the eye of the camera's plane of focus (dioptres) (L < 0) GH the pupil diameter (mm) e the eccentricity of the flash source from the camera aperture (mm). M magnification of the image measured relative to the camera plane of locus [ABSTRACT FROM AUTHOR]

The direction of chromostereopsis observed with a natural pupil and the direction of the monocularly perceived disparity between coloured targets (F and C lines - 486 and 656 nm) have been measured in a sample of 30 subjects at 10 and 1000 lx. At both illumination levels approximately equal numbers of subjects perceived positive and negative chromostereopsis. When the ambient illumination was increased, a reversal in the direction of the chromostereopsis occurred for 16 subjects. For six of them a change from a positive to a negative chromostereopsis was observed, a pattern not reported in previous studies. In most cases at both high and low illuminance, there was an absence of perception of a monocular disparity (transverse chromatic aberration), although chromostereopsis was reported, indicating that binocular information can be obtained from sub-threshold monocular disparities. At low illuminance, the lack of correlation between the direction of chromostereopsis and transverse chromatic aberration (TCA) may indicate that there may be a supplementary binocular factor in chromostereopsis. [ABSTRACT FROM AUTHOR]