Movement disorders consist of a diverse and heterogeneous group of neurological impairments, frequently accompanied by abnormalities in ocular motility and visual perception. Parkinson’s disease is one of the more common and is caused by degeneration of dopaminergic neurons in the substantia nigra of the midbrain with loss of dopamine terminals in the basal ganglia. It is regarded primarily as a disorder of the motor system with bradykinesia, rigidity, and tremor as its main features. However, autonomic, cognitive, and sensory symptoms frequently occur as well.
Visual disturbance is not considered to be one of the cardinal clinical symptoms of Parkinson’s disease even though blurred vision, photophobia, asthenopia (weakness or fatigue of the eyes, usually accompanied by headache and dimming of vision), or trouble reading are common, often significantly interfering with the patient’s quality of life.(1,2) Visual problems have particular significance because of the Parkinson patient’s impaired mobility and the implications for driving safety. In most cases, however, gross eye examination appears normal. Nonetheless, several papers have been published describing ophthalmological abnormalities, including problems with visual function, ocular movements, and visual hallucinations, as well as complications of drug therapy or neurosurgical interventions. We will review these in this article.
Ocular discomfort and pain
The most common ocular complaints are the result of ocular surface irritation, including blepharitis and xerophthalmia (dry eyes). Blepharitis is often responsible for ocular pain;(3) dry eyes can cause itching, burning, irritation, and blurred vision that may improve with blinking. Unfortunately, spontaneous blinking is impaired, leading to discomfort, particularly after periods of reading, watching TV, or computer use. Blepharitis can cause excessive tearing, but most studies show decreased lacrimal flow in Parkinson patients, reflecting autonomic dysfunction.(2,4)
The decreased blink rate, a classical manifestation of Parkinson’s disease, (5) is likely to worsen any discomfort from dry eyes, because the main function of blinking is to maintain the tear film in front of the cornea. Treatment with artificial tears can help when a patient has these complaints.(3)
Visual acuity and colour vision
The disease process itself does not impair visual acuity but subclinical impairment of colour vision, especially in the blue-green axis, has been described. (6) The retina, which is part of the central nervous system, has many intrinsic neurotransmitters. Amacrine cells in the retina (fig 1) have been shown to use dopamine as a neurotransmitter. These cells have far reaching dendrites that contact cone bipolar cells, in addition to synapsing with other amacrine cells that are part of the rod pathways. Thus, dopaminergic amacrine cells are involved in both rod and cone pathways, but their precise function is still unknown. (7)
Figure 1 Retinal layers—the arrow shows the dopaminergic amacrine cells.
Reduced visual contrast sensitivity has also been reported (6) and this too may be related to retinal dopaminergic dysfunction. However, it is claimed that the visual abnormality is orientation specific (affecting horizontal stimulus gratings more than vertically orientated gratings): this implicates dysfunction of the visual cortex in addition to the retina. (8)
Ocular and visual symptoms in parkinson’s disease
Ocular itching, burning, irritation, discomfort, and pain
Dry eyes
Excessive tearing
Photophobia
Asthenopia (weakness or fatigue of the eyes, usually accompanied by headache and dimming of vision)
Trouble reading and blurred vision
Visual hallucinations
The abnormalities of colour vision as well as the contrast sensitivity defect seem to be related to the severity of the disease (9) and can be partially corrected by treatment with L-dopa (11) or the direct dopamine receptor agonist, apomorphine. (12) Interestingly, L-dopa has recently been reported to improve visual acuity in amblyopic subjects, but the mechanism is not clear.
Visual hallucinations
Visual hallucinations are common in Parkinson’s disease, occurring in 25–40% of patients.(14) They most frequently report the sensation that another person is present when they are not, or describe the sensation of a person or an animal moving past the periphery of their visual field. These hallucinations usually last for only a few seconds to a minute or so. Most patients are elderly and other causes such as decreased visual acuity due to cataract or macular degeneration may contribute to the hallucinations. Visual hallucinations can thus be attributed to decreased visual acuity, cognitive impairment, and/or medications such as dopaminergics and anticholinergics. (10,14) Interestingly, as many as 10% of patients experiencing visual hallucinations also have auditory hallucinations.
The pathogenesis of the hallucinations is unknown, and the precise role of dopamine and antiparkinsonian drug treatment has been debated.(15,16) Using positron emission tomography (PET) and fluorodeoxyglucose, Nagano-Saito et al (17) noted increased cerebral glucose metabolic rate in patients with visual hallucinations, especially in the left superior frontal gyrus (fig 2) with relative hypometabolism in the posterior area. They suggested that this was the likely metabolic correlate of visual hallucinations, though what this actually means is still not clear. Williams and Lees (18) have recently suggested that the visual hallucinations are due to nerve cell loss and Lewy body pathology in the ventral temporal regions of the brain.
Figure 2 Fluorodeoxyglucose positron emission tomography shows increase in cerebral metabolism in the frontal areas in Parkinson’s disease patients with visual hallucinations.
In most cases the hallucinations are “benign”. Typically, patients are aware that the images are not real. Nevertheless, the hallucinations may be very unpleasant and disturb not only the patient’s quality of life but also, and sometimes to an even greater degree, their carers’. Like other psychotic states, the hallucinations usually resolve following treatment with neuroleptics. However, most of these agents cannot be used because they usually exacerbate the motor symptoms of Parkinson’s disease. In this situation atypical neuroleptics, particularly clozapine and seroquel, may be better tolerated. (19)
Visual fields
The visual fields are typically normal. Surgical procedures such as pallidotomy may damage neighbouring structures, such as the optic radiation or the optic tract, often resulting in a contralateral superior quadrantanopia in 5–10% of patients (due to a lesion affecting Meyer’s loop that traverses the temporal lobe). The quadrantanopia is usually asymptomatic and is rarely noticed by the patient. (20)
Ocular movements
Superficial oculomotor examination in Parkinson patients is usually normal. Nevertheless, a more detailed examination can reveal subtle abnormalities (see table 1). These include slow, hypometric saccades (especially vertically) in certain situations, most notably saccades made to the remembered location of a target after it has been extinguished (“remembered saccades”). (21,22) Although vertical gaze abnormalities have been associated with the disease, limited upgaze is common in the elderly and this is therefore a non-specific sign. (23,24) Clinically, hypometric movements can often be made more obvious by asking patients to refixate alternately between two stationary targets.
TABLE 1 Ocular motor deficits in Parkinson’s disease Smooth pursuit movements are also usually impaired during tracking of a moving target. The pursuit gain (eye velocity/target velocity) is decreased, and thus the eyes move a little slower than the target, necessitating catch-up saccades. This results in what is referred to as “cogwheel pursuit” (25,26) though the pathogenesis of this phenomenon is quite different from that of cogwheeling felt in the limbs. Visual fixation may be disrupted by square wave jerks, small back-to-back involuntary saccades which cause the eyes to move briefly away from the target before returning back to it again. Square wave jerks are, however, not specific and may occur in normal individuals and in many other conditions such as cerebellar disorders and progressive supranuclear palsy.
The hallucinations may be very unpleasant and disturb not only the patient’s quality of life but also, and sometimes to an even greater degree, their carers Saccade amplitudes are improved 90 minutes after a single oral dose of L-dopa. (24) Similarly, general clinical improvement of parkinsonian features following treatment with dopaminergic drugs is associated with an improvement of saccadic accuracy and smooth pursuit gain. (25) These results suggest possible dopaminergic involvement in the control of some ocular movements, but the precise nature of this involvement has not yet been clarified.
Impaired convergence is also common, helping to explain the high prevalence of asthenopia and reading difficulties in patients with Parkinson’s disease. Defective accommodation is in many cases due to pharmacological therapy, notably anticholinergic drugs which relax the ciliary muscles thereby impairing the ability of the eyes to focus (accommodate).
Abnormal eyelid movements
In addition to the reduced spontaneous blinking, other eyelid abnormalities such as blepharo-spasm and apraxia of eyelid opening have been reported in advanced Parkinson patients.(1,6,27) Infrequent blinking contributes to the characteristic expressionless stare, often with a blink rate as low as 1–2 per minute (compared to normal blinking of 16–18 per minute).(5) A wide eyed appearance is common in progressive supranu-clear palsy, whereas Parkinson patients frequently have a mild apparent ptosis, sometimes mimicking myasthenia.
Electrophysiology
Electrophysiological studies have shown delays in visual evoked potentials (VEP) and amplitude reduction in electroretinograms (ERG). (27,28) The amplitudes of both a and b waves of the ERG are reduced, possibly due to an abnormality in the dopaminergic pathway of the retina described above. (29,30) Bodis Wollner and colleagues were the first to report that the latency of the P100 component of pattern reversal VEP was prolonged, (30,31) and this has been confirmed in subsequent studies.(32) It has been suggested that these VEP defects are a result of the reduced dopamine levels in the amacrine cells. (29–33)
Pupillary abnormalities
Various pupillary abnormalities have been described but it is unclear if they are caused by the disease itself or the pharmacological treatment. Micieli et al found abnormally slow pupillary responses to light and pain, (34-35) Applying pharmacological agents to patients’ eyes confirmed that the peripheral autonomic nervous system was intact (35) suggesting that the pupillary abnormalities result from central autonomic dysfunction, particularly in the parasympathetic Edinger-Westphal nucleus of the midbrain.(36)
confirming previous studies which found that resting pupil diameters were normal, but responses to changes in light were reduced.
Conclusions
Although Parkinson’s disease is mainly a motor disorder, patients frequently complain of impaired vision and difficulty in reading, despite normal visual acuity.
Local ocular discomfort is often the result of local ocular problems such as blepharitis or reduced blinking, and is often helped by treatment with artificial tears.
Other visual abnormalities are usually clinically silent and are not likely to be noticed during a routine neurological examination or on ordinary visual acuity testing.
Other than cogwheel smooth pursuit, obvious oculomotor abnormalities in a patient thought to have Parkinson’s disease should suggest alternative diagnoses such as progressive supranuclear palsy.
Visual hallucinations are not uncommon, and may be helped by treatment with atypical neuroleptics.
Acknowledgements
Reviewed by Dr Christian Lueck, Canberra.
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Clinical Sciences 