Abstract
Purpose :
It is possible to find biomarkers in the retina that inform about the pathological state of other parts of the body. Neurodegenerative diseases could be diagnosed early by high-precision retinal imaging. However, many cells in the inner retina are too transparent to be detected by existing techniques. We have shown how multi-offset detection in Adaptive Optics Scanning Laser Ophthalmoscopy (AO-SLO) can capture variations in refractive index between retinal cells leading to images of ganglion and microglial cells in humans in vivo. A detector with the same offset distance was installed on a custom-modified AO-SLO Optical Coherence Tomography (OCT) device. The aim of this project was to detect transparent cellular biomarkers on patients suffering from multiple sclerosis (MS).
Methods :
Images were acquired with the AO-SLO-OCT using a split-detector at 10 ADD offset distance. We imaged a total of 35 participants, 10 controls and 25 patients with MS. From the 25 patients, 20 were included in a therapeutic protocol, targetting patients with optic neuritis (ON) who received an electrical stimulation of the optic nerve; the other 5 patients (4 without ON) were included in an observational protocol. Patients were followed over several months and were imaged over different time periods. Quantitative biomarkers such as cell density, cell size and motion speed were extracted over time. AOSLO images were co-localized with simultaneously acquired AO-OCT cross sections to determine the retinal depth of cells.
Results :
Inflammatory cells were detected on the retinal ganglion cell layer (GCL) in MS patients. We determined their depth through AO-OCT where highly reflective spots corresponded to the cells observed on the AOSLO images. The cell density peaked right after the ON and decreased over the following weeks. Cells were also detected on the control eye with no ON from the patients undergoing therapy and a few isolated cells were detected on some observational patients.
Conclusions :
These cells specifically detected in the GCL which is targeted by MS degeneration, with a density that varies over time in relation to symptomatic attacks of the disease are a quantifiable biomarker of the state of the inflammation and could be correlated with other changes in this layer caused by MS. We aim to use this biomarker to evaluate the influence of the inflammatory response in MS on the demyelination process.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.