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.