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Eye tremors are pervasive in Parkinson's disease and could be an early warning sign of the neurodegenerative movement disorder, according to a case-control study.

All 112 Parkinson's patients tested, including newly diagnosed cases not yet on medication, showed constant small rhythmic movements of their eyes when attempting to fix their gaze on an object, Mark S. Baron, MD, of the VA Medical Center in Richmond, Va., and colleagues found.

By comparison, the same fixation instability was seen in just two of 60 age-matched controls, one of whom apparently had presymptomatic Parkinson's disease based on symptoms that developed over 2 years of follow up, the group reported online in the Archives of Neurology.

"The pervasiveness and specificity of this feature suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson's disease," the group wrote.

As a simple screening test, it could be nearly 100% accurate, whereas even specialists are wrong in diagnosing Parkinson's about 15% of the time with when they first see someone with tremor, Baron said in an interview.

That will be key to identifying who could benefit from treatment as new options are developed that can slow progression of the disease, he told 番茄社区.

The movements are too small to notice clinically and require specialty equipment to measure, Baron noted.

However, 63% of the Parkinson's patients had fixation instability that moved their focus enough on occasion to reach the 0.5° threshold thought to create problems with vision.

"We do know that people often complain of blurred vision with Parkinson's disease, but no one's been able to explain why," Baron told 番茄社区. "We believe this is probably a major reason."

In the study, the researchers used a video-based system that rests on the head and tracks the center of the pupil with infrared lights and cameras.

Among the 112 Parkinson's patients recruited from the Richmond VA's center for Parkinson's research and treatment, 94 were on dopaminergic medications and had shown benefit. The rest were de novo untreated.

Altogether, this group had persistent problems with fixation stability. The oscillations had:

• A mean frequency of 5.7 Hz (ranging from 4.3 to 10.9 Hz)
• A mean amplitude of 0.27° horizontally and 0.33° vertically (range from 0.14° to 1.63°)

For individual patients, the frequency of these ocular tremors appeared stable, never varying by more than 1 Hz, though the amplitude fluctuated in a regular pattern.

Head movements didn't contribute to these findings, nor did saccades, blinks, or other eye movements change the ocular tremor. Saccades are small, jerky movements of the eyes when a person changes focus from one point to another. Fixation instability did not correlate with duration or severity of disease or dopa-equivalent dosing either.

Medicated and unmedicated patients didn't differ in fundamental frequency, magnitude of the oscillations, or in fixation instability as measured by root mean square velocity while fixing the gaze on a target.

"The fact that this behavior was universally observed in every tested patient with Parkinson's disease, including unmedicated patients, suggests that ocular tremor is a function of the disease process and not induced by medication," Baron's group wrote.

However, the Parkinson's disease patients did differ compared with the 60 age-matched controls recruited from among patients' family and friends, among whom just 3.3% showed similar oscillatory fixation instability.

The root mean square velocity during fixation was 5.72°/s with Parkinson's versus 3.07°/s among controls (P<0.001). Absolute mean velocities also differed between the groups (3.11 versus 1.80°/s, respectively, P<0.001).

Whereas some prior studies had suggested that saccades accounted for the main abnormalities, Baron's study indicated no difference in those parameters for externally-driven reflexive saccades compared with controls.

Nor were there differences in the brief, random movements away from the visual target called square wave jerks that some other studies showed. Square wave jerks are brief, conjugate, random movements away from the target that interrupt stable fixations, according to the authors.

The fixation problems in Parkinson's somewhat resembled the involuntary rapid eye movements of pendular nystagmus (fast, uncontrollable eye movements), but with greater complexity and smaller magnitude of movement not reset by saccades, suggesting it is an ocular tremor rather than pendular nystagmus, the researchers argued.

They cautioned that their study could not separate out the extent to which individual parkinsonian medications may have influenced the results, nor could it correlate fixation instability with actual visual function.

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