Adaptive Optics Retinal Imaging in Multiple Sclerosis
Abstract
Development of medications that may protect neurons or replace myelin in multiple sclerosis (MS) at a rapid pace requires effective models and biomarkers. While some medications have successfully done so in cell culture and animal models, the same medications often fail in humans. For this reason, patient-based biomarkers are needed to better develop targeted treatments. In this application, we will propose a novel, innovative approach for direct, in vivo measurement of neuronal cell integrity in MS. This proposal thus directly targets the FY21 MSRP Focus Area Central Nervous System Regenerative Potential in Demyelinating Conditions, subheading Development of biomarkers of repair. Precise measures of neuronal integrity in living MS patients are the most direct means by which to evaluate the efficacy of future therapeutics aimed at remyelination and neuroprotection/neural repair. This will be achieved using a prototype eye imaging device that uses adaptive optics (AO) in combination with scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) to obtain images of the retina at such fine resolution that we are able to visualize, count, and measure individual neuron and inflammatory cell bodies and bundles of axons. Here we propose a study in which 30 MS patients that have experienced optic neuritis (ON) in the past, 30 MS patients that have not experienced ON, and 20 healthy controls will undergo scanning on the AO device. We will measure and count individual retinal ganglion cells (RGC, a type of neuron in the retina), axonal bundles (the processes that extend from the RGCs), and retinal macrophages (a type of inflammatory cell). We will compare the measurements of these cell types among the three groups and will relate inflammatory cell measurements to neuronal measurements. We anticipate that this study will demonstrate that patients with MS have loss of neurons and axons that are visualized directly with AO retinal imaging and that these cell losses will be directly related to inflammatory cell presence/activity. It is expected that if we can validate this technology as a means by which to directly measure these cell types in a living patient with MS, AO retinal imaging could be used in the future as a direct biomarker in studies of medications aimed at neuronal protection, neuronal repair, and replacement of lost myelin. What types of patients could it potentially help and how? This study has relevance to MS patients of all types. We envision that the AO technique could be used in future trials of remyelination or neuronal protection medications for those experiencing an attack of ON. If successful, medications of that type could be useful in relapsing MS patients for prevention of vision loss or other relapse symptoms. We also envision the technique could be utilized in a long-term study of neuronal protection or remyelination in patients with progressive MS subtypes, which is a population in dire need of therapies to restore function or prevent disability. What are the potential clinical applications, benefits, and risks? The AO technique is envisioned initially to be most useful in the research arena, helping to spur faster and more efficient drug development for MS. This will have a direct clinical benefit on MS patients. The AO technique is not likely to translate well, at least initially, to the clinic as a tool for use by clinicians. However, with future improvements in technology, this may one day become feasible. No risks to the technique have thus far been observed or are anticipated. What is the projected time it may take to achieve a patient-related outcome? As the AO device is a prototype, we envision that this grant would serve as the necessary first step in a multi-step, multi-year process required to achieve patient-related outcomes. This proposed study would take 3 years to complete. After this validation, we anticipate the need for further study in
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210995
Entities
People
- Daniel Harrison
Organizations
- United States Army
- University of Maryland, Baltimore