April 11, 2012 — Ocular tremors may provide an early biomarker for diagnosis of Parkinson's disease (PD), a new study suggests.
Using precise eye-tracking technology, researchers found ocular fixation instability in all 112 patients with PD they tested, compared with only 2 of 60 healthy age-matched controls. One of the patients showed parkinsonian features at the 2-year follow-up examination.
Precise oculomotor testing "could provide clinicians with a simple means to accurately diagnose Parkinson's disease, with accuracy well exceeding that of clinical assessments," Mark S. Baron, MD, from the Southeast Parkinson's Disease Research, Education, and Clinical Center, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, who worked on the study, told Medscape Medical News.
He noted that testing for fine ocular instability is "straight forward and can be routinely done," adding: "I do believe this could become standard of care."
The study was published online April 9 in Archives of Neurology.
In a telephone interview with Medscape Medical News, Andrew D. Siderowf, MD, MSCE, associate professor of neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, who was not involved in the study, said he's "impressed" by the data.
"People don't typically think of Parkinson's patients as having fixation impairment and all of the Parkinson's patients had this abnormality," he commented.
Pervasive, Specific Feature
Several studies have described various oculomotor abnormalities in patients with PD, although conflicts remain about specific deficits, the study team notes in their paper. The inability to critically fixate on an object has been subjectively described in PD, but "its pervasiveness had not been previously recognized nor had it been systematically quantified," they point out.
Dr. Baron said the current study originated as an extension of the early expertise of Paul A. Wetzel, PhD, from the Department of Biomedical Engineering at Virginia Commonwealth University in Richmond, who has used eye-movement tracking to train US Air Force pilots.
The study included 112 patients with PD (mean age, 66 years) and 60 age-matched controls. Ninety-four of the patients with PD had a clear therapeutic response to dopaminergic medications and 18 were de novo untreated patients. The patients had had PD symptoms for an average of 5.5 years. They had a mean Unified Parkinson's Disease Rating Scale (UPDRS) part III score of 12.1 and a mean tremor subscore of 2.2.
The investigators report that while fixating on a randomly displaced target on a computer screen, all 112 patients with PD showed persistent instability characterized by oscillatory behavior, with a mean fundamental frequency of 5.7 Hz, ranging from 4.3 to 10.9 Hz.
In contrast, 58 of the 60 controls (96.6%) showed highly stable fixations characterized by minimal drift of gaze and no oscillatory behavior. The remaining 2 controls had oscillatory fixation instability on par with that of the patients with PD, and 1 has since developed parkinsonian symptoms.
Effect on Foveal Vision
The investigators say the mean amplitude of the fixation instability was 0.27 degree horizontally and 0.33 degree vertically, ranging from 0.14 to 1.63 degrees. They say the vertical component of the instability was of greater magnitude than the horizontal component in 92 of the 112 patients with PD (82.1%). In 71 patients (63.3%), the maximum amplitude of the instability at times reached the 0.5-degree threshold for obscuring foveal vision.
"Patients with PD often present to ophthalmologists with complaints of poor vision." Dr. Baron commented. "They however are not tested for fine ocular instability and so are routinely erroneously told that there is not a clear problem to account for their complaints."
The study authors say the fixation instability in PD partially resembles that of pendular nystagmus, "but with notable differences. Although the fundamental frequency of the wave-form and the consistency of the fundamental frequency in each patient are consistent with that of pendular nystagmus, the complexity and smaller magnitude of the waveforms in PD differ substantially from that generally characteristic of pendular nystagmus," they write.
The study team didn't find any correlation between amplitude and frequency of fixation instability and disease duration, clinical UPDRS scores, or dopa-equivalent dosing. In addition, the oculomotor measures did not differ between medicated and unmedicated patients, "suggesting that ocular tremor is a function of the disease process and not induced by medication," they say. They caution, however, that they couldn't ascertain the extent to which individual medications may have influenced the results.
Dr. Baron said, "Now that we have identified the problem, we need to next correlate the ocular deficits with subjective complaints and with objective visual deficits. Also, we need to assess whether specific medications worsen or benefit the underlying problem," he added.
Immediate Clinical Implications
There were also no between-group differences in saccadic measures and occurrences of square wave jerks. The findings "affirm that reflexive saccades remain universally normal in PD," the investigators say.
"Since reflexive saccades, as well as square wave jerks, are regularly abnormal in other movement disorders, these features could potentially serve as a valuable means to differentiate PD from other conditions," they write.
Dr. Siderowf noted that the technology used in the study "was more sophisticated and more sensitive to these relatively subtle abnormalities." Still, "it's probably something that wouldn't be terribly expensive to implement. I actually think it would be relatively simple and it could be used for better and earlier diagnosis and screening maybe for candidates for some of these new [imaging] scans that are coming out."
The study was supported by the Department of Veterans Affairs. The authors and Dr. Siderowf have disclosed no relevant financial relationships.
Arch Neurol. Published online April 9, 2012. Abstract
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