8 research outputs found
Retinal phenotyping of variants of Alzheimer's disease using ultra-widefield retinal images
Background: Posterior cortical atrophy (PCA) is the most common atypical variant of Alzheimer's disease (AD). Changes associated with PCA in the brain affect the visual cortex, but little is known about retinal changes in PCA. In this study, we explored retinal phenotypic variations in typical AD (tAD) and PCA. Methods: Retinal phenotyping was carried out on ultra-widefield (UWF) images of 69 control, 24 tAD, and 25 PCA participants. Results: Individuals with tAD (odds ratio [OR]Â =Â 2.76 [confidence interval (CI):1.24 to 6.10], PÂ =Â .012) and PCA (ORÂ =Â 3.40 [CI:1.25 to 9.22], PÂ =Â .016) were more likely phenotyped as hard drusen. tAD (ORÂ =Â 0.34 [CI:0.12 to 0.92], PÂ =Â .035) were less likely to have soft drusen compared to control. Almost 3-fold increase in reticular pseudodrusen formation in tAD (ORÂ =Â 2.93 [CI:1.10 to 7.76], PÂ =Â .030) compared to control was estimated. Discussion: Studying the peripheral retina may contribute to a better understanding of differences in retinal phenotypes of different AD variants
Optic nerve thinning and neurosensory retinal degeneration in the rTg4510 mouse model of frontotemporal dementia
Visual impairments, such as difficulties in reading and finding objects, perceiving depth and structure from motion,
and impaired stereopsis, have been reported in tauopathy disorders, such as frontotemporal dementia (FTD). These
impairments however have been previously attributed to cortical pathologies rather than changes in the neurosensory
retina or the optic nerve. Here, we examined tau pathology in the neurosensory retina of the rTg(tauP301L)4510
mouse model of FTD. Optic nerve pathology in mice was also assessed using MRI, and corresponding measurements
taken in a cohort of five FTD sufferers and five healthy controls. rTg(tauP301L)4510 mice were imaged (T2-weighted
MRI) prior to being terminally anesthetized and eyes and brains removed for immunohistochemical and histological
analysis. Central and peripheral retinal labelling of tau and phosphorylated tau (pTau) was quantified and retinal layer
thicknesses and cell numbers assessed. MR volumetric changes of specific brain regions and the optic nerve were
compared to tau accumulation and cell loss in the visual pathway. In addition, the optic nerves of a cohort of healthy
controls and behavioural variant FTD patients, were segmented from T1- and T2-weighted images for volumetric study.
Accumulation of tau and pTau were observed in both the central and peripheral retinal ganglion cell (RGC), inner
plexiform and inner nuclear layers of the neurosensory retina of rTg(tauP301L)4510 mice. This pathology was
associated with reduced nuclear density (− 24.9 ± 3.4%) of the central RGC layer, and a reduced volume (− 19.3 ± 4.6%)
and elevated T2 signal (+ 27.1 ± 1.8%) in the optic nerve of the transgenic mice. Significant atrophy of the cortex
(containing the visual cortex) was observed but not in other area associated with visual processing, e.g. the lateral
geniculate nucleus or superior colliculus. Atrophic changes in optic nerve volume were similarly observed in FTD
patients (− 36.6 ± 2.6%). The association between tau-induced changes in the neurosensory retina and reduced optic
nerve volume in mice, combined with the observation of optic nerve atrophy in clinical FTD suggests that ophthalmic
tau pathology may also exist in the eyes of FTD patients. If tau pathology and neurodegeneration in the retina were to
reflect the degree of cortical tau burden, then cost-effective and non-invasive imaging of the neurosensory retina
could provide valuable biomarkers in tauopathy. Further work should aim to validate whether these observations are
fully translatable to a clinical scenario, which would recommend follow-up retinal and optic nerve examination in FT
The effects of zinc supplements on primary human foetal retinal pigment epithelium in culture.
Supplementary Material for: Peripheral Retinal Imaging Biomarkers for Alzheimer’s Disease: A Pilot Study
<b><i>Purpose:</i></b> To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer’s disease (AD) and its progression. <b><i>Methods:</i></b> Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student <i>t</i> test and the χ<sup>2</sup> test. <b><i>Results:</i></b> Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ<sup>2</sup> = 9.9, df = 4, <i>p</i> = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10<sup>–3</sup> ± 2.865 × 10<sup>–3</sup> vs. 6.375 × 10<sup>–3</sup> ± 1.532 × 10<sup>–3</sup>, <i>p</i> = 0.008; entire image: 8.235 × 10<sup>–3</sup> ± 2.839 × 10<sup>–3</sup> vs. 6.050 × 10<sup>–3</sup> ± 1.414 × 10<sup>–3</sup>, <i>p</i> = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, <i>p</i> = 0<b><i>.</i></b>049) with a trend for both at FU. <b><i>Conclusions:</i></b> UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL<sub></sub> and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring
Recent Developments of Retinal Image Analysis in Alzheimer’s Disease and Potential AI Applications
Alzheimers disease (AD) is the most common progressive neurodegenerative illness and cause of dementia in the elderly. The critical barriers for primary prevention in AD are the lack of rapid, non-invasive, sensitive and low-cost biomarkers. As the eye and brain share essential structural and pathogenic pathways, non-invasive eye biomarkers could be identified to obtain new insights into the onset and progression of AD and its complications in the eye. In this short review, recent developments of retinal image analysis in AD and potential artificial intelligence (AI) applications are presented. Some approaches are still very much novel research techniques, others are more established and transitioning into the clinical diagnostic arena. Together they provide us with the capability to move AD detection research forwards by using novel peripheral biomarkers