Fixational microsaccades: A quantitative and objective measure of disability in multiple sclerosis.

BACKGROUND: Objective tools for prognosis and disease progression monitoring in multiple sclerosis (MS) are lacking. The visuomotor system could be used to track motor dysfunction at the micron scale through the monitoring of fixational microsaccades. AIMS: The aim of this study was to evaluate whether microsaccades are correlated with standard MS disability metrics and to assess whether these methods play a predictive role in MS disability. METHOD: We used a custom-built retinal eye tracker, the tracking scanning laser ophthalmoscope (TSLO), to record fixation in 111 participants with MS and 100 unaffected controls. RESULTS: In MS participants, a greater number of microsaccades showed significant association with higher Expanded Disability Status Scale score (EDSS, p < 0.001), nine-hole peg test (non-dominant: p = 0.006), Symbol Digit Modalities Test (SMDT, p = 0.014), and Functional Systems Scores (FSS) including brainstem (p = 0.005), cerebellar (p = 0.011), and pyramidal (p = 0.009). Both brainstem FSS and patient-reported fatigue showed significant associations with microsaccade number, amplitude, and peak acceleration. Participants with MS showed a statistically different average number (p = 0.020), peak vertical acceleration (p = 0.003), and vertical amplitude (p < 0.001) versus controls. Logistic regression models for MS disability were created using TSLO microsaccade metrics and paraclinical tests with ⩾80% accuracy. CONCLUSION: Microsaccades provide objective measurements of MS disability level and disease worsening.

Intact globe inflation testing of changes in scleral mechanics in myopia and recovery.

The purpose of this study was to examine the effects of myopia-inducing and myopia recovery conditions on the scleral biomechanics of enucleated eyes of young chicks. Enucleated eyes from 5-day old chicks, with fiducial markers attached at 5 locations on the external sclera, were placed in a custom-built chamber filled with phosphate-buffered saline, and subjected to controlled increments in intraocular pressure (IOP). IOP was initially ramped from 15 to 100 mmHg and then maintained at 100 mmHg for one hour, with eyes photographed at a rate of 0.1 Hz over the same period. There were two experimental groups, one in which chicks were monocularly form deprived for four days to induce myopia, and the other in which chicks were allowed two days of recovery from myopia induced by two days of form deprivation. For all chicks, the contralateral (fellow) eyes served as controls. Myopic eyes showed less initial deformation relative to their fellows, while no difference was recorded between recovering eyes and their fellows over the same time frame. With exposure to sustained elevated pressure, eyes in all groups displayed time-dependent changes in creep behavior, which included a linear region of secondary, steady creep. The creep deformation of myopic eyes was significantly higher than that of their fellows, consistent with results of previous studies using uniaxial loading of scleral strips. When allowed only 2 days to recover from induced myopia, previously myopic eyes continued to show increased creep deformation. Compared to results reported in studies involving scleral strips, our whole globe testing yielded higher values for creep rate. Whole globe inflation testing provides a viable, less anatomically disruptive and readily adaptable method for investigating scleral biomechanics than uniaxial tensile strip testing. Furthermore, our results suggest that elastic stretching does not contribute to the increased axial elongation underlying myopia in young chick eyes. They also confirm the very limited involvement of the sclera in the early recovery from myopia, reflecting the well documented lag in scleral versus choroidal recovery responses.

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.

Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis.

Neurodegeneration mediates neurological disability in inflammatory demyelinating diseases of the CNS. The role of innate immune cells in mediating this damage has remained controversial with evidence for destructive and protective effects. This has complicated efforts to develop treatment. The time sequence and dynamic evolution of the opposing functions are especially unclear. Given limits of in vivo monitoring in human diseases such as multiple sclerosis (MS), animal models are warranted to investigate the association and timing of innate immune activation with neurodegeneration. Using noninvasive in vivo retinal imaging of experimental autoimmune encephalitis (EAE) in CX3CR1GFP/+-knock-in mice followed by transcriptional profiling, we are able to show 2 distinct waves separated by a marked reduction in the number of innate immune cells and change in cell morphology. The first wave is characterized by an inflammatory phagocytic phenotype preceding the onset of EAE, whereas the second wave is characterized by a regulatory, antiinflammatory phenotype during the chronic stage. Additionally, the magnitude of the first wave is associated with neuronal loss. Two transcripts identified - growth arrest-specific protein 6 (GAS6) and suppressor of cytokine signaling 3 (SOCS3) - might be promising targets for enhancing protective effects of microglia in the chronic phase after initial injury.