Ocular Motor Abnormalities in Neurodegenerative Disorders

CA Antoniades; C Kennard


Eye. 2015;29(2):200-207. 

In This Article

Parkinson's Disease

Idiopathic PD (IPD) is a progressive neurodegenerative disorder that results in a loss of dopamine in the basal ganglia giving rise to tremor, rigidity, bradykinesia, and postural instability.

Clinical Ocular Motor Findings

Ocular motor abnormalities that might be detected during a routine clinical examination include blepharospasm, paucity of blinking, apraxia of lid opening, visual neglect, reduced vergence, reduced upgaze, and blurred vision.[34]

Research Findings

Abnormalities of eye movements, especially in saccades are known to occur in PD. To date, several studies have presented quantitative data from studying different types of saccadic eye movements in PD, but early results were conflicting. Although some authors found that saccadic velocity was preserved,[35,36] others did not.[37,38] As pointed out,[36] these discrepancies could have been attributed to methodological differences. In most studies, the patients were taking various antiparkinsonian drugs that we now know may have profound effects on eye movements.

Typically, even at the earlier stages of the disease, the most consistent ocular motor abnormality in PD is saccadic hypometria in which the primary saccade undershoots the target, especially vertically.[39–41] This was initially demonstrated in saccades executed to verbal command,[42] in the dark,[43] or to fixed targets.[37] Predictive saccades also show hypometria, in addition to difficulty in anticipating the stimulus,[36,44] and in unilaterally affected patients the abnormalities were found to be lateralized.[45] There are also deficits in initiation and performance of internally mediated tasks, including antisaccades and memory-tasks.[40,44,46–48] The memory-guided task seems to be the most sensitive, and performance gets worse as disease progresses.[46,47,49–51] Mild to moderate PD patients show a marked increase in saccade amplitudes.[52] Saccadic latency is typically normal or mildly increased compared with controls.[36,38,53]

Studies of scanpaths of saccades during visuospatial sorting tasks have provided insights into the cognitive changes in PD.[4] In the 'Tower of London' task, that tests working memory and planning, patients have to rearrange coloured balls to fit a particular pattern. After analysing the scanpaths of PD patients in this task compared with those of controls, it was suggested that PD patients kept forgetting the arrangement of the test objects,[54] implying a deficiency in their spatial working memory.[55]

Advanced PD patients may show greater abnormalities on particular tests as compared with mild PD patients.[5] For example, they make more directional errors in the antisaccade task and have increased mean latencies[53] that increase as the disease progresses;[48] this is more evident when patients are on anticholinergic medication.[56] It has been suggested that in advanced PD, brain structures other than the basal ganglia such as the frontal lobe,[57] might produce these saccadic deficits.

If endogenously and exogenously driven saccades are differentially affected in PD, a task such as the antisaccade paradigm that involves both should demonstrate impairment. Some studies have found no significant impairment in the performance of PD patients compared with age-matched controls,[47,58] and others have shown impaired performance.[48,53,56,59,60] It is difficult to draw firm conclusions from these studies because of methodological difficulties; however, the one study that employed a 'gap' paradigm and tested patients in their 'OFF' state, demonstrated more errors, increased latency, and reduced gain in patients with mild to moderate PD,[59] compared with controls. However, if reflexive (pro-) and antisaccade tasks are mixed up in a block, as opposed to the usual single-task blocks normally used, then PD patients showed a marked increase in prosaccade and antisaccade error rates in repeated trials.[61]

Response to Treatment

Studies looking into the effect of L-dopa are not consistent and sometimes even conflicting, which may be owing to an inadequate number of subjects studied. A few studies have shown beneficial effects on the parameters of voluntary saccades,[39,42] and on the ability to perform sequences of MGS,[49] but none has ever demonstrated any improvement in the most characteristic abnormality in PD, the hypometria of MGS. Recent studies have agreed that L-dopa and dopamine agonists shorten the latency of these voluntary saccades,[62,63] whereas they prolong the latency of both externally guided or triggered saccades.[64]

Several studies have examined the effect of STN stimulation on saccades. Stimulation of the STN reduced reflexive saccadic latencies,[3,65] increased the amplitude,[66,67] and produced a marked improvement in the gain of MGS.[68] There is also a single case report of a similar improvement in MGS, as well as antisaccades, in a patient with a GPi electrode when the stimulator is turned on.[69] Depending on the location of the electrode fixation instability may occur.[70] A disruption of ocular fixation has also been reported after a unilateral pallidotomy.[71]

Differential Diagnosis

Clinically obvious impairment in vertical eye movements is a characteristic of PSP, although it may be seen in other conditions such as diffuse Lewy body disease,[8] CBD,[72] amyotrophic lateral sclerosis,[73] post-encephalitic parkinsonism,[74] and Creutzfeld–Jacob disease.[75] In PSP, slowing of vertical saccades precedes ophthalmoplegia and is probably the earliest sign of ocular motor involvement. A supranuclear gaze palsy may be seen in CBD, but usually only when the disease is advanced.[76] Eye signs are rarely an early feature of MSA, but in some cases may mimic PD.

Several studies are using eye movements to differentiate parkinsonian-like syndromes, although it is still not clear to what extent eye movement recordings are helpful in discriminating among them. A couple of small studies have examined simple saccadic metrics in the horizontal, vertical, and diagonal planes in patients with PD, MSA, pure akinesia, PSP,[77] and CBD.[41] It was found that compared with age-matched controls only patients with PSP had slow saccades (in any direction), and only patients with CBD had increased saccadic latency. Other parameters such as hypometria, vestibulo-ocular responses, and smooth pursuit did not discriminate between groups, although deviation of oblique saccades towards the horizontal plane was more marked in patients with pure akinesia and PSP. In another study,[58] patients with CBD had greater saccadic latency, and those with PSP more marked hypometria and worse antisaccade performance compared with patients with PD, however, there were no saccadic criteria by which patients with MSA could be differentiated from those with PD. Thus detailed eye movement analysis may be helpful in identifying patients with PSP and possibly CBD, but until there is more data on its sensitivity and specificity using large prospectively studied patient cohorts, it is difficult to recommend it for routine use in the diagnosis of parkinsonian disorders.