Andrew Kadis from Cambridge Vision Technology guides us through imaging technologies for retinal biomarkers in Alzheimer’s disease
Cambridge Vision Technology provides AI-based technology for early detection of Alzheimer’s Disease Dementia using ocular biomarkers. Here, they detail the underlying clinical science and technology, explaining why the retina is an ideal target for diagnostic efforts. The article reviews the retinal biomarkers linked to the disease
and details the imaging hardware associated with enabling this innovative screening method.
Overview
Detecting Alzheimer’s disease (AD) early is becoming increasingly important with the arrival of new treatments, such as Lecanemab (Leqembi) and Donanemab (Kisunla). These new therapies are disease-modifying treatments (DMTs) that need to be administered early to be effective. Early detection maximises efficacy, helping individuals maintain cognitive function longer and better manage their overall health.
The retina offers a compelling and practical way to screen for early signs of AD. The eye is the only part of the brain that can be directly imaged non- invasively, making it an ideal target for accessible and early diagnostic tools. Retinal imaging technologies are already widely used in optometrists and eye care clinics; this is a promising location for early-stage AD screening.
This article explores the underlying clinical science and associated imaging hardware. First, we discuss the retinal features associated with AD, detailing the structural, vascular, and molecular biomarkers. We then detail the associated imaging technologies that capture this detail, many of which are already widely deployed.
Biomarkers
Scientific research has extensively documented the changes in the retina associated with AD, offering valuable insights into its early detection. These changes can be grouped into structural, vascular, and molecular biomarkers, each reflecting underlying neurodegenerative and vascular processes linked to AD.
Structural biomarkers are among the most established indicators. The thinning of the retinal nerve fibre layer (RNFL), is a key marker of AD. This layer, comprising the axons of retinal ganglion cells, shows significant thinning as neuronal and synaptic loss progresses in the brain. Similarly, atrophy in the ganglion cell-inner plexiform layer (GC-IPL), composed of neurons critical for signal transmission, provides another robust marker of neurodegeneration.
Vascular biomarkers also play a significant role, offering valuable insights into AD. One prominent indicator is reduced fractal density, a measure of the branching complexity of retinal vasculature. This reduction reflects vascular degeneration and diminished blood flow efficiency, which are hallmark features of AD. Additional structural changes, such as altered vessel diameter ratios and increased vascular tortuosity, further indicates irregularities in the retinal vascular network.
Imaging the blood flow directly through emerging technologies like Optical Coherence Tomography Angiography (OCTA) has uncovered further vascular biomarkers. Reduced capillary density, a hallmark of vascular impairment in AD, indicates disruptions in the retina’s microvascular health. Enlargement of the foveal avascular zone (FAZ), a normally small capillary-free area, provides further evidence of compromised blood supply. These vascular changes collectively underscore the retina’s potential as a critical site for identifying early signs of AD and monitoring disease progression.
Finally, molecular biomarkers have gained prominence with recent technological advancements. Hyperspectral imaging studies have identified amyloid-beta deposits in the retina, and their presence is well-established. Additionally, early tau protein aggregation have also been observed in retinal layers, although further validation is needed.
Imaging technologies for retinal biomarkers in Alzheimer’s disease
Here, we provide a brief overview of the relevant posterior (back of the eye) imaging technologies starting with the most commonly deployed to the least. All of the below show some level of sensitivity to detecting the appropriate AD biomarkers detailed above.
Fundus imaging involves capturing 2D images of the back of the retina to visualise its structure and vasculature. Standard fundus imaging uses a retinal camera, while Scanning Laser Ophthalmoscopy (SLO) employs laser scanning for enhanced detail and contrast. Both of these technologies provide direct imaging of vascular biomarkers in AD. Fundus imaging systems are widely deployed in clinical settings, making them highly suitable for large-scale screenings and triaging.
Optical Coherence Tomography (OCT) is a non-invasive imaging technology that creates cross-sectional retina images
at micrometre-level resolutions. OCT captures volumetric sections of the retina, providing detailed insights into its structure. For AD, OCT effectively measures structural biomarkers such as RNFL and GC-IPL atrophy.
Traditionally confined to hospital settings, OCT is now much more widely available and is present in most optometrists. In the UK, the National Health Service (NHS) has just recently expanded its digital eye screening programme to include OCT scans.
Hyperspectral imaging analyses the retina across a broad spectrum of wavelengths, capturing detailed biochemical data. This technology holds significant promise for detecting molecular biomarkers either through direct imaging or using spectrographic signatures. While still an emerging technology in Ophthalmology, its high sensitivity makes it a compelling tool for early detection, and several innovative systems are now being introduced to the market.
OCTA builds on OCT by adding angiography capability to directly image blood flow at the back of the retina. It enables direct visualisation of further vascular biomarkers, such as reduced capillary density and enlargement of the FAZ. Although its adoption in clinical settings is still growing, it is expected to become increasingly prevalent as its diagnostic value becomes more widely recognised.
Conclusion: Technologies to fight neurodegenerative diseases
From the above, it is clear that the technology building blocks for early detection of Dementia are already established. In this article, we have detailed the various underlying biomarkers and discussed the various technological imaging options, many of which are already widely deployed. Using the eye for early detection of AD is an enticing idea, garnering greater traction in the wider community. Retinal imaging for early detection
of AD promises to be a valuable tool in the fight against neurodegenerative diseases alongside emerging technologies such as cognitive tests, blood biomarkers and new therapies.
This work is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International.
