ABSTRACT
Objective: Saccadic Intrusions (SIs) are abnormal eye movements during gaze fixation. Studies have indicated the clinical relevance of SIs, especially of square wave jerks (SWJ) in ALS. We used a software-based platform to extract SIs as a part of an interventional drug trial. The objective was to examine SIs' change over time as a potential biomarker of ALS disease progression. Methods: 28 ALS patients (61.95 ± 8.6 years) were assessed with the revised ALS Functional Rating Scale (ALSFRS-R) and with an oculometric test. Changes of SIs over time and correlations with ALSFRS-R and its bulbar subscale were calculated. A power calculation was conducted to understand the practical implications of results. Results: A significant increase of SWJ over trial duration was observed, with an increase in frequency (mean rise of 0.14 ± 0.28, p < 0.01), amplitude (0.001 ± 0.0016 degrees, p < 0.005), overall duration of SWJ (0.13 ± 0.25, in %, p < 0.01), and in their relative part out of all intrusions (0.18 ± 0.32, in %, p < 0.005). Negative correlations were found with the bulbar subscale (R=-0.43, -0.41, -0.39 and -0.47, respectively, p < 0.001). The required sample size for observing a 40% reduction in bulbar aspects when using the oculometric test (α = 0.05 and ß = 0.8), was found to be 150 patients per arm, compared with 200 patients using the bulbar subscale. Conclusions: Evaluation of saccadic intrusions during fixation was able to detect disease progression over time, correlated with ALSFRS-R bulbar subscale. Eye movements can potentially serve as an objective biomarker in ALS clinical trials and reduce the required sample size to show clinical effect of therapies.
ABSTRACT
Objective: Oculometric measures (OM) can be extracted from eye movements during presentation of visual stimuli. Studies have indicated the benefit of OM in assessment of neurological disorders, including Amyotrophic Lateral Sclerosis (ALS). We used a new software-based platform for the extraction of OM during patients' assessment. Our objective was to examine the correlation between OM and clinical assessment as a part of a clinical drug trial. Methods: 32 ALS patients (mean age 60.75 ± 10.36 years, 13 females), were assessed using a validated score (ALSFRS-R), and a novel software-based oculometric platform (NeuraLight, Israel) as a part of a clinical drug trial. Correlations of ALSFRS-R with OM were calculated and compared with matched healthy subjects' data (N = 129). Results: A moderate correlation was found between ALSFRS-R and corrective saccadic latency (R = 0.52, p = 0.002). Fixation time during smooth pursuit and peak velocity during pro-saccades were both worse in ALS patients versus healthy subjects (mean (SD)=0.34(0.06) vs. 0.3(0.07), p = 0.01, and 0.41(0.05) vs. 0.38(0.07), p = 0.04, respectively). Patients with bulbar symptoms (N = 14) had a decreased pro-saccade gain compared with patients without bulbar symptoms (mean (SD)=0.1 (0.04) vs. 0.93 (0.07), p = 0.01), and a larger error rate of anti-saccade movement (mean (SD)=0.42 (0.21) vs. 0.28 (0.16), p = 0.04). Conclusions: Oculometric measures correlated with the clinical assessment and were different from data of healthy subjects. Further studies are warranted to establish the role of oculometrics in the evaluation of patients with ALS and other neurodegenerative disorders, and its possible use in clinical trials.
