A practical approach to functional optical coherence tomography shows abnormal retinal responses in Alzheimer’s disease

Spectral-domain optical coherence tomography (SD-OCT) is an accessible
clinical tool for measuring structural changes to the retina, and
increasingly as a biomarker for brain-predominant neurodegenerative
diseases like Alzheimer’s. Information about retinal function can also be
extracted from OCT images, but is under-studied, with literature examples
often employing challenging protocols or requiring specialized hardware.
The first goal of this study was to verify that functional retinal imaging
was feasible with a commercially-available SD-OCT device and a clinically
practical protocol. Inspired by methods from other functional imaging
modalities, we acquired images while repeatedly cycling lights on and off,
and spatially normalized retinas to facilitate intra- and inter-individual
analyses. In eight healthy young adults, light-dependent increases in
reflectivity were easily demonstrated at photoreceptor inner and outer
segments, changing by ~7% in bright light and ~3% in dim light. Bright
light elicited a subtle (~2%) but consistent light-dependent decrease in
reflectivity through much of the rest of the retina, including the
avascular outer nuclear layer (ONL). We speculated that some of these
changes are influenced by glial function – as through water management – a
topic of high interest in neurodegenerative diseases that may involve the
glymphatic system. Functional abnormalities in patients with antibodies
against aquaporin-4 (n=3) supported this interpretation. We next compared
patients with early-onset Alzheimer’s disease (n=14) to age-matched
controls (n=14), revealing that patients had a relatively exaggerated
light-induced change in ONL reflectivity (p<0.05). Because these
measurements can be obtained within thirty minutes, regular use in
research and limited clinical settings is feasible.