Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.

Characterizing Fixational Eye Motion Variance Over Time as Recorded by the Tracking Scanning Laser Ophthalmoscope.

PURPOSE: The purpose of this study was to characterize the benign biological variance of fixational microsaccades in a control population using a tracking scanning laser ophthalmoscope (TSLO), accounting for machine accuracy and precision, to determine ideal testing conditions to detect pathologic change in fixational eye motion (FEM). METHODS: We quantified the accuracy and precision of the TSLO, analyzing measurements made by three operators on a model eye. Repeated, 10-second retinal motion traces were then recorded in 17 controls, 3 times a day (morning, afternoon, and evening), on 3 separate days. Microsaccade metrics (MMs) of frequency, average amplitude, peak velocity, and peak acceleration were extracted. Trace to trace, interday, and intraday variability were calculated across all subjects. RESULTS: Intra-operator and machine variation contributed minimally to total variation, with only 0.007% and 0.14% contribution for frequency and amplitude respectively. Bias was detected, with lower accuracy for higher amplitudes. Participants had an average (SD) microsaccade frequency of 0.84 Hz (0.52 Hz), amplitude of 0.32 degrees (0.11 degrees), peak velocity of 43.68 degrees/s (14.02 degrees/s), and peak acceleration of 13,920.04 degrees/s2 (4,186.84 degrees/s2). The first trace recorded within a session significantly differed from the second two in both microsaccade acceleration and velocity (P < 0.05), and frequency was 0.098 Hz higher in the evenings (P < 0.05). There was no MM difference between days and no evidence of a session-level learning effect (P > 0.05). CONCLUSIONS: The TSLO is both accurate and precise. However, biological inter- and intra-individual variance is present. Trace to trace variability and time of day should be accounted for to optimize detection of pathologic change.

Trainee and Program Director Perspectives on Meaningful Patient Attribution and Clinical Outcomes Data.

BACKGROUND: The Accreditation Council for Graduate Medical Education specifies that trainees must receive clinical outcomes and quality benchmark data at specific levels related to institutional patient populations. Program directors (PDs) are challenged to identify meaningful data and provide them in formats acceptable to trainees. OBJECTIVE: We sought to understand what types of patients, data/metrics, and data delivery systems trainees and PDs prefer for supplying trainees with clinical outcomes data. METHODS: Trainees (n = 21) and PDs (n = 12) from multiple specialties participated in focus groups during academic year 2017-2018. They described key themes for providing clinical outcomes data to trainees. RESULTS: Trainees and PDs differed in how they identified patients for clinical outcomes data for trainees. Trainees were interested in encounters where they felt a sense of responsibility or had autonomy/independent decision-making opportunities, continuity, or learned something new; PDs used broader criteria including all patients cared for by their trainees. Both groups thought trainees should be given trainee-level metrics and consistently highlighted the importance of comparison to peers and/or benchmarks. Both groups found value in "push" and "pull" data systems, although trainees wanted both, while PDs wanted one or the other. Both groups agreed that trainees should review data with specific faculty. Trainees expressed concern about being judged based on their patients' clinical outcomes. CONCLUSIONS: Trainee and PD perspectives on which patients they would like outcomes data for differed, but they overlapped for types of metrics, formats, and review processes for the data.