Fixational eye movements following concussion.

The purpose of this study was to evaluate fixational eye movements (FEMs) with high spatial and temporal resolution following concussion, where oculomotor symptoms and impairments are common. Concussion diagnosis was determined using current consensus guidelines. A retinal eye-tracking device, the tracking scanning laser ophthalmoscope (TSLO), was used to measure FEMs in adolescents and young adults following a concussion and in an unaffected control population. FEMs were quantified in two fixational paradigms: (1) when fixating on the center, or (2) when fixating on the corner of the TSLO imaging raster. Fixational saccade amplitude in recent concussion patients (≤ 21 days) was significantly greater, on average, in the concussion group (mean = 1.03°; SD = 0.36°) compared with the controls (mean = 0.82°; SD = 0.31°), when fixating on the center of the imaging raster (t = 2.87, df = 82, p = 0.005). These fixational saccades followed the main sequence and therefore also had greater peak velocity (t = 2.86, df = 82, p = 0.006) and peak acceleration (t = 2.80, df = 82, p = 0.006). These metrics significantly differentiated concussed from controls (AUC = 0.67-0.68, minimum p = 0.005). No group differences were seen for the drift metrics in either task or for any of the FEMs metrics in the corner-of-raster fixation task. Fixational saccade amplitudes were significantly different in the concussion group, but only when fixating on the center of the raster. This task specificity suggests that task optimization may improve differentiation and warrants further study. FEMs measured in the acute-to-subacute period of concussion recovery may provide a quick (<3 minutes), objective, sensitive, and accurate ocular dysfunction assessment. Future work should assess the impact of age, mechanism of injury, and post-concussion recovery on FEM alterations following concussion.

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.

Methods to Assess Ocular Motor Dysfunction in Multiple Sclerosis.

: BACKGROUND:: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system causing the immune-mediated demyelination of the brain, optic nerve, and spinal cord and resulting in ultimate axonal loss and permanent neurological disability. Ocular motor dysfunction is commonly observed in MS but can be frequently overlooked or underappreciated by nonspecialists. Therefore, detailed and quantitative assessment of eye movement function has significant potential for optimization of patient care, especially for clinicians interested in treating visual symptoms or tracking disease progression. METHODS:: A brief history of eye tracking technology followed by a contextualized review of the methods that can be used to assess ocular motor dysfunction in MS-including a discussion of each method's strengths and limitations. We discuss the rationale for interest in this area and describe new tools capable of tracking eye movements as a possible means of monitoring disease. RESULTS/CONCLUSIONS:: This overview should inform clinicians working with patients with MS of how ocular motor deficits can best be assessed and monitored in this population. It also provides a rationale for interest in this field with insights regarding which techniques should be used for studying which classes of eye movements and related dysfunction in the disease.

Advantages of Lissamine Green Vital Staining as an Endpoint in Dry Eye Clinical Trials.

Purpose: The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials. Methods: Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects. Inclusion was based on reported symptoms, lissamine green (LG) conjunctival staining, Fluorescein (Fl) corneal and conjunctival staining, and Schirmer's Test (ST). Outcome measures were assessed based on the modifiability of LG staining to exposure to a Controlled Adverse Environment (CAE®), correlation of LG to Fl staining, relative variation of LG staining scores and Schirmer test scores, and the correlation of LG staining with symptom scores. Results: The modifiability of LG conjunctival staining to environmental exposure was demonstrated, with nasal LG and FL staining displaying the most similar percent change. Nasal LG conjunctival staining scores for subjects with ST scores of less than 8mm were significantly higher than for subjects with ST greater than 8mm. LG staining scores were more consistent (25% change from baseline threshold) than ST scores. Finally, statistically significant correlations were found between LG staining and a number of symptom scores. Conclusion: This evaluation demonstrates the superiority of the utilization of a clinical endpoint focused on ocular surface damage. The reproducibility and modifiability of LG conjunctival staining to controlled adverse environment, coupled with its significant correlation with symptoms, positions it as an exemplary clinical sign endpoint for clinical management and in clinical trials. Our findings advocate for the adoption of LG conjunctival staining as a primary endpoint in both clinical research and drug development, offering a more effective means of identifying and addressing ocular surface damage in the realm of DED.

Patches of Dysflective Cones in Eyes With No Known Disease.

Purpose: To characterize the structure and function of patches of dysflective cones in the foveal region of subjects with normal vision and no known pathology. Dysflective cones are cones that have little or no reflective properties in optical coherence tomography (OCT) or adaptive optics scanning laser ophthalmoscope (AOSLO) images yet exhibit measurable function. Methods: AOSLO images were surveyed for the presence of hyporeflective cone patches, and subjects were brought back for imaging to determine the changes in the hyporeflective region. Adaptive optics microperimetry (AOMP) was used to assess the function of hyporeflective patches in four subjects to determine that they did, in fact, contain dysflective cones. AOMP utilized a stimulus size of less than 1 arcmin to measure thresholds inside and outside the hyporeflective region. Results: Nineteen out of 47 individuals retrospectively reviewed had one or more regions with hyporeflective cone patches in one or both eyes. Ten subjects with hyporeflective cone patches were brought back for imaging. Seven of the 10 had resolved at follow up, and in three subjects new hyporeflective patches appeared in a different location. All AOMP-measured subjects had measurable function in the dysflective cone region. Three out of four subjects showed no difference in light sensitivity in the dysflective region compared to adjacent areas, and one subject showed a 3× reduction in sensitivity in the area. Conclusions: Patches of dysflective cone have been identified in subjects with normal vision and no known pathology, and we have observed instances where dysflective cones in these subjects regain normal reflective properties.

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.

Comparing Cone Structure and Function in RHO- and RPGR-Associated Retinitis Pigmentosa.

Purpose: To study cone structure and function in patients with retinitis pigmentosa (RP) owing to mutations in rhodopsin (RHO), expressed in rod outer segments, and mutations in the RP-GTPase regulator (RPGR) gene, expressed in the connecting cilium of rods and cones. Methods: Four eyes of 4 patients with RHO mutations, 5 eyes of 5 patients with RPGR mutations, and 4 eyes of 4 normal subjects were studied. Cone structure was studied with confocal and split-detector adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography. Retinal function was measured using a 543-nm AOSLO-mediated adaptive optics microperimetry (AOMP) stimulus. The ratio of sensitivity to cone density was compared between groups using the Wilcoxon rank-sum test. Results: AOMP sensitivity/cone density in patients with RPGR mutations was significantly lower than normal (P < 0.001) and lower than patients with RHO mutations (P < 0.015), whereas patients with RHO mutations were similar to normal (P > 0.9). Conclusions: Retinal sensitivity/cone density was lower in patients with RPGR mutations than normal and lower than patients with RHO mutations, perhaps because cones express RPGR and degenerate primarily, whereas cones in eyes with RHO mutations die secondary to rod degeneration. High-resolution microperimetry can reveal differences in cone degeneration in patients with different forms of RP.

Loss of Foveal Cone Structure Precedes Loss of Visual Acuity in Patients With Rod-Cone Degeneration.

Purpose: To assess the relationship between cone spacing and visual acuity in eyes with rod-cone degeneration (RCD) followed longitudinally. Methods: High-resolution images of the retina were obtained using adaptive optics scanning laser ophthalmoscopy from 13 eyes of nine RCD patients and 13 eyes of eight healthy subjects at two sessions separated by 10 or more months (mean 765 days, range 311-1935 days). Cone spacing Z-score measured as close as possible (average <0.25°) to the preferred retinal locus was compared with visual acuity (letters read on the Early Treatment of Diabetic Retinopathy Study [ETDRS] chart and logMAR) and foveal sensitivity. Results: Cone spacing was significantly correlated with ETDRS letters read (ρ = -0.47, 95%CI -0.67 to -0.24), logMAR (ρ = 0.46, 95%CI 0.24 to 0.66), and foveal sensitivity (ρ = -0.30, 95%CI -0.52 to -0.018). There was a small but significant increase in mean cone spacing Z-score during follow-up of +0.97 (95%CI 0.57 to 1.4) in RCD patients, but not in healthy eyes, and there was no significant change in any measure of visual acuity. Conclusions: Cone spacing was correlated with visual acuity and foveal sensitivity. In RCD patients, cone spacing increased during follow-up, while visual acuity did not change significantly. Cone spacing Z-score may be a more sensitive measure of cone loss at the fovea than visual acuity in patients with RCD.