Tremor of the Eyes, or of the Head, in Parkinson's Disease?

Recently, Gitchel et al. reported that “pervasive ocular tremor” is present in patients with Parkinson’s disease (PD) while they attempt steady visual fixation. This was a universal finding in the 112 PD patients that they studied, but was generally absent from their 60 healthy control subjects. This finding of a pervasive ocular tremor in PD has generated substantial interest but also controversy, as is evident by the article by Kaski et al., and the ensuing correspondence by Baron et al. in the current issue of Movement Disorders. Because pervasive ocular tremor might provide a most useful biomarker for PD, it seems justified to examine the validity of the measurements of Gitchel et al. and consider alternative explanations for their results, before they gain wide acceptance and application. Here we summarize some of the evidence for and against the case for pervasive ocular tremor in PD, and suggest future experiments to resolve conflicting opinions. First, consider the visual requirements of eye movements during attempted fixation of a stationary, highcontrast visual target, such as a letter X. One requirement is that the image of the target of interest must be held on the foveal region of the retina (an area subtending about 0.5 degrees in diameter, which has the highest visual acuity). An additional requirement for clear vision is that the image must not move more than about 5 degrees/s over the retina, or visual acuity will decline and observers will perceive illusory motion of the target (oscillopsia). Second, consider how well normal healthy subjects can hold their gaze still when they visually fixate a small, stationary target and their head is immobilized (best achieved using a custom-made bite-bar). During such conditions, a subject’s gaze (line of sight with respect to the earth) is not perfectly still, but is disrupted by 3 distinct perturbations: microtremor, microsaccades, and drifts of the eyes. Microtremor has dominant frequencies averaging approximately 84 Hz and ranging from 70 Hz to 103 Hz. Due to its high frequency (much greater than frequencies achieving perceptual flicker fusion) and very small amplitude ( 1 photoreceptor width, <0.5 arcmin), microtremor is thought to have little influence on vision. Microsaccades are rapid movements, typically less than 1 degree in size with frequencies of 1 to 2 Hz, which appear to play an important role in counteracting perceptual fading during fixation. Recent work suggests that square-wave intrusions, so common in patients with movement disorders, lie on a continuum with microsaccades. Smooth intersaccadic drifts during attempted fixation are thought to be under the control of smooth eye movements, and typically do not exceed 0.1 degrees/s, unless visual feedback is interrupted, for example, by switching the environment to darkness. When all these “fixational eye movements” are taken into account, the standard deviation of gaze is typically <0.2 degrees, so the eyes are not perfectly still, but the image of an object of interest spends most of its time on the fovea. (One must keep in mind the possibility of foveal visual impairment in PD, however, which might affect fixation behavior.) If the subject’s head is now free to move, gaze stability also depends on the vestibulo-ocular reflex, which compensates (although not perfectly) for head perturbations. If the vestibulo-ocular reflex is absent, even transmitted cardiac pulsations can disrupt vision, because the direction of gaze now depends on head position. Blurred vision and oscillopsia also occur when abnormal eye movements, such as acquired pendular nystagmus, induce retinal image motion that exceeds 5 degrees/s. With this background, we can now ask: What manner of eye movements have Gitchel et al. discovered to be present in every Parkinsonian patient whose gaze they measured during visual fixation? They -----------------------------------------------------------*Correspondence to: Dr. R. John Leigh, M.D. Department of Neurology, Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106; [email protected]