Ocular Tremor a Possible Biomarker for Early Parkinson’s Disease

Ocular fixation instability, also known as ocular tremor, is a pervasive and highly specific feature among patients with Parkinson’s disease, according to findings from a study involving 112 patients and 60 controls.

The findings suggest that modern, precise eye tracking technology for assessing oculomotor parameters could facilitate diagnosis of Parkinson’s disease at an early stage, according to George T. Gitchel of Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va., and his colleagues. The report was published online April 9 in Archives of Neurology.

All of the 112 Parkinson’s disease patients in the study showed persistent oscillatory fixation instability during testing with a video-based binocular eye tracker, compared with only 2 control subjects – including 1 control subject with “apparently presymptomatic Parkinson disease.” Both medicated and nonmedicated patients had the abnormality.

The current findings are the first to thoroughly describe and confirm the pervasiveness of fixation instability in Parkinson’s disease patients, they said.

“The fact that this behavior was universally observed in every tested patient with Parkinson’s disease, including nonmedicated patients, suggests that ocular tremor is a function of the disease process and not induced by medication,” they added.

The mean fundamental frequency of the oscillatory behavior was 5.7 Hz; the mean amplitude of the fixation instability in patients was 0.27 degrees horizontally and 0.33 degrees vertically (Arch. Neurol. 2012 April 9 [doi:10.1001/archneurol.2012.70]).

“In 71 subjects, the maximum amplitude of the instability at times reached the 0.5 degree estimated threshold for obscuring foveal vision,” the investigators said, noting that magnetic head tracking in a subset of patients affirmed that head movements did not contribute to the instability.

The investigators measured significant differences between the Parkinson’s disease group and the control group in the mean root mean square (RMS) velocity during fixation (5.72 degrees per second vs. 3.07 degrees per second, respectively), as well as in the absolute mean velocity (3.11 degrees per second vs. 1.80 degrees per second).

None of the measured fixation parameters correlated with Unified Parkinson’s Disease Rating Scale part III examination scores, tremor subscores, or disease duration, and no differences were seen between 94 medicated and 18 nonmedicated patients with respect to fundamental frequency, magnitude, or RMS velocity of ocular tremor. Saccadic latency to step-displaced random targets and saccadic amplitude, velocity, and duration also did not differ between the Parkinson’s disease patients and the controls.

The mean age of patients in this study, who were recruited from the Southeast Parkinson’s Disease Research, Education, and Clinical Center at the Richmond Veterans Affairs Medical Center, was 66.2 years, and mean duration of symptoms was 5.5 years. Control subjects were recruited among the spouses, relatives, and friends of patients.

Although previous studies have shown that neurodegenerative changes in the brain in patients with Parkinson’s disease affect the oculomotor control system, conflicts regarding findings of specific deficits have remained unresolved.

“Some investigators have suggested that the principle abnormalities are reduced velocity and increased duration of saccades, while others have suggested that the frequency of square wave jerks (brief, conjugate, random movements away from the target that interrupt stable fixations) are increased,” the investigators wrote. While deficits in ocular fixation have been subjectively described in Parkinson’s disease, they have not been systematically quantified, they said.

The findings also indicate that the fixation instability seen in Parkinson’s disease patients does not represent pendular nystagmus, although the instability associated with each condition shares some features. Notable differences, however, include greater complexity and smaller magnitude of the waveforms in Parkinson’s disease, compared with the general characteristics of pendular nystagmus, and more chaotic instability with multiple sinusoid frequency components in Parkinson’s disease, compared with the typically purely sinusoidal pendular nystagmus.

The findings are limited by an inability to determine the extent to which individual medication might have influenced the findings and by the lack of a formal objective test of visual acuity, which curtailed the investigators’ ability to directly correlate the extent of fixation instability with actual visual function.

This study was supported by the Department of Veterans Affairs. The authors had no disclosures to report.

 

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