Introduction The eye offers potential for the diagnosis of Alzheimer’s disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. Methods In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460–620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. Results Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60–0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. Conclusions This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

The timely detection of neurodegenerative diseases is central to improving clinical care as well as enabling the development and deployment of disease-modifying therapies. Retinal imaging is emerging as a method to detect features of a number of neurodegenerative diseases, given the anatomical and functional similarities between the retina and the brain. This review provides an overview of the current status of retinal imaging biomarkers of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Huntington's disease and multiple sclerosis. Whilst research findings are promising, efforts to harmonise study designs and imaging methods will be important in translating these findings into clinical care. Doing so may mean that eye care providers will play important roles in the detection of a variety of neurodegenerative diseases in future.

Purpose: Hyperspectral imaging is gaining attention in the biomedical field because it generates additional spectral information to study physiological and clinical processes. Several technologies have been described; however an independent, systematic literature overview is lacking, especially in the field of ophthalmology. This investigation is the first to systematically overview scientific literature specifically regarding retinal hyperspectral imaging. Methods: A systematic literature review was conducted, in accordance with PRISMA Statement 2009 criteria, in four bibliographic databases: Medline, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Results: Fifty-six articles were found that meet the review criteria. A range of techniques was reported: Fourier analysis, liquid crystal tunable filters, tunable laser sources, dualslit monochromators, dispersive prisms and gratings, computed tomography, fiber optics, and Fabry-Perrot cavity filter covered complementary metal oxide semiconductor. We present a narrative synthesis and summary tables of findings of the included articles, because methodologic heterogeneity and diverse research topics prevented a meta-analysis being conducted. Conclusions: Application in ophthalmology is still in its infancy. Most previous experiments have been performed in the field of retinal oximetry, providing valuable information in the diagnosis and monitoring of various ocular diseases. To date, none of these applications have graduated to clinical practice owing to the lack of sufficiently large validation studies. Translational Relevance: Given the promising results that smaller studies show for hyperspectral imaging (e.g., in Alzheimer's disease), advanced research in larger validation studies is warranted to determine its true clinical potential.