Reflections on the Utility of the Retina as a Biomarker for Alzheimer's Disease: A Literature Review.

As a part of the central nervous system, the retina may reflect both physiologic processes and abnormalities related to diseases of the brain. Indeed, a concerted effort has been put forth to understand how Alzheimer's disease (AD) pathology may manifest in the retina as a means to assess the state of the AD brain. The development and refinement of ophthalmologic techniques for studying the retina in vivo have produced evidence of retinal degeneration in AD diagnosed patients. In this review, we will discuss retinal imaging techniques implemented to study the changes in AD retina as well as highlight the recent efforts made to correlate such findings to other clinical hallmarks of AD to assess the viability of the retina as a biomarker for AD

Volumetric microvascular imaging of human retina using optical coherence tomography with a novel motion contrast technique

Phase variance-based motion contrast imaging is demonstrated using a spectral domain optical coherence tomography system for the in vivo human retina. This contrast technique spatially identifies locations of motion within the retina primarily associated with vasculature. Histogram-based noise analysis of the motion contrast images was used to reduce the motion noise created by transverse eye motion. En face summation images created from the 3D motion contrast data are presented with segmentation of selected retinal layers to provide non-invasive vascular visualization comparable to currently used invasive angiographic imaging. This motion contrast technique has demonstrated the ability to visualize resolution-limited vasculature independent of vessel orientation and flow velocity

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious

In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography

We present in vivo volumetric images of human retinal micro-circulation using Fourier-domain optical coherence tomography (Fd-OCT) with the phase-variance based motion contrast method. Currently fundus fluorescein angiography (FA) is the standard technique in clinical settings for visualizing blood circulation of the retina. High contrast imaging of retinal vasculature is achieved by injection of a fluorescein dye into the systemic circulation. We previously reported phase-variance optical coherence tomography (pvOCT) as an alternative and non-invasive technique to image human retinal capillaries. In contrast to FA, pvOCT allows not only noninvasive visualization of a two-dimensional retinal perfusion map but also volumetric morphology of retinal microvasculature with high sensitivity. In this paper we report high-speed acquisition at 125 kHz A-scans with pvOCT to reduce motion artifacts and increase the scanning area when compared with previous reports. Two scanning schemes with different sampling densities and scanning areas are evaluated to find optimal parameters for high acquisition speed in vivo imaging. In order to evaluate this technique, we compare pvOCT capillary imaging at 3x3 mm^2 and 1.5x1.5 mm^2 with fundus FA for a normal human subject. Additionally, a volumetric view of retinal capillaries and a stitched image acquired with ten 3x3 mm^2 pvOCT sub-volumes are presented. Visualization of retinal vasculature with pvOCT has potential for diagnosis of retinal vascular diseases

Optical coherence tomography and scanning laser ophthalmoscopy: Approaches to dual-channel retinal tissue imaging

We report a Talbot bands-based optical coherence tomography (OCT) system capable of producing longitudinal B-scan OCT images and en-face scanning laser ophthalmoscopy (SLO) images of the human retina in-vivo, with various degrees of simultaneity

Differential intensity contrast swept source optical coherence tomography for human retinal vasculature visualization

We demonstrate an intensity-based motion sensitive method, called differential logarithmic intensity variance (DLOGIV), for 3D microvasculature imaging and foveal avascular zone (FAZ) visualization in the in vivo human retina using swept source optical coherence tomog. (SS-OCT) at 1060 nm. A motion sensitive SS-OCT system was developed operating at 50,000 A-lines/s with 5.9 μm axial resoln., and used to collect 3D images over 4 mm^2 in a normal subject eye. Multiple B-scans were acquired at each individual slice through the retina and the variance of differences of logarithmic intensities as well as the differential phase variances (DPV) was calcd. to identify regions of motion (microvasculature). En face DLOGIV image were capable of capturing the microvasculature through depth with an equal performance compared to the DPV

Retinal biomarkers of Alzheimer’s disease: insights from transgenic mouse models

In this paper, we use the retina as a window into the central nervous system and in particular to assess changes in the retinal tissue associated with the Alzheimer’s disease. We imaged the retina of wild-type (WT) and transgenic mouse model (TMM) of Alzheimer’s disease with optical coherence tomography and classify retinas into the WT and TMM groups using support vector machines with the radial basis function kernel. Predictions reached an accuracy over 80% at the age of 4 months and over 90% at the age of 8 months. Texture analysis of computed fundus reference images suggests a more heterogeneous organization of the retina in transgenic mice at the age of 8 months in comparison to controls.This study was supported by the Neuroscience Mantero Belard Prize 2015 (Santa Casa da Misericórdia)(MB-1049-2015), by The Portuguese Foundation for Science and Technology (PEst-UID/NEU/04539/2013), by FEDER-COMPETE (POCI-01-0145-FEDER-007440) and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020).info:eu-repo/semantics/publishedVersio

In vivo human retinal and choroidal vasculature visualization using differential phase contrast swept source optical coherence tomography at 1060 nm

A differential phase contrast (DPC) method is validated for in vivo human retinal and choroidal vasculature visualization using high-speed swept-source optical coherence tomography (SS-OCT) at 1060 nm. The vasculature was identified as regions of motion by creating differential phase variance (DPV) tomograms: multiple B-scans were collected of individual slices through the retina and the variance of the phase differences was calculated. DPV captured the small vessels and the meshwork of capillaries associated with the inner retina in en face images over 4 mm^2 in a normal subject. En face DPV images were capable of capturing the microvasculature and regions of motion through the inner retina and choroid