Diagnosis and Treatment of Neuro-Ophthalmologic Symptoms in People with Parkinson Disease

Although the motor symptoms of Parkinson disease (PD) are well-recognized, increasing attention is being directed toward the nonmotor manifestations of PD, including ocular and visual disturbances. These symptoms—such as abnormal eye movements, convergence insufficiency, visual hallucinations, eyelid opening apraxia, dry eyes, and retinal changes—can emerge early in the disease course and may serve as valuable PD clinical indicators or biomarkers. Ocular complications related to deep brain stimulation (DBS) may also occur. Understanding these neuro-ophthalmologic features of PD supports early detection and disease monitoring. Increased awareness and collaboration across specialties can lead to tailored treatments and improve the quality of life (QoL) of people with PD.

Abnormal Eye Movements
Abnormal eye movements, which have been extensively documented in PD, have been better characterized through advanced eye-tracking technologies. These abnormalities include saccades, smooth pursuit, and fixation.

Saccades are rapid, ballistic eye moments that quickly shift gaze between 2 visual targets. Different kinds of saccades are distinguished by their mode of initiation—command, by verbal cues; self-paced, by voluntary timing; reflexive, by sudden target appearance; and memory-guided, by memory of target locations. PD most commonly impairs self-paced and memory-guided saccades.¹ Saccadic abnormalities in PD adversely affect QoL by disrupting tasks such as turning, thereby increasing instability and fall risk.² Reading—another key daily activity—is also impaired, with individuals demonstrating slower reading speeds.³

People with PD often exhibit reduced smooth pursuit (ie, continuous gaze tracking of a slowly moving target) gain in which the eyes lag behind the target, resulting in imprecise tracking.⁴ In addition, people with PD may display saccadic pursuit, where tracking is intermittently interrupted by small, corrective saccades.⁴ Smooth pursuit abnormalities in PD correlated with disease severity in some studies, but not with core motor symptoms or dopaminergic therapy, which suggests that smooth pursuit abnormalities are caused by executive dysfunction.⁴

Fixation abnormalities in PD often involve an increased frequency and amplitude of square wave jerks (SWJs). SWJs are saccadic intrusions that cause brief deviations away from a fixation point followed by corrective saccades. SWJs are more frequent and pronounced in people with PD compared with healthy controls, and can cause oscillopsia, a disturbing perception of visual motion.⁵

These oculomotor abnormalities stem from basal ganglia dysfunction and impaired cortical–subcortical integration. Excess inhibitory output from the substantia nigra pars reticulata disrupts superior colliculus activity, impairing saccadic generation. Frontal eye field dysfunction also contributes to these deficits.⁶

Convergence Insufficiency
Convergence refers to the coordinated inward movement of both eyes allowing fusion of 2 retinal images into a single binocular image during near tasks such as reading. Convergence insufficiency impairs this coordination, leading to diplopia (double vision), blurred vision, visual fatigue, and lacrimation.

Convergence insufficiency affects ~31.3% of people with PD, compared with 7.5% of age-matched controls.⁷ Dopaminergic dysfunction is believed to play a role in this disparity.⁸ Although diplopia is a classic symptom of convergence insufficiency, many individuals report more subtle symptoms or avoid near tasks without recognizing the underlying cause.⁷

Evidence for treating convergence insufficiency in PD is limited. Prism therapy (ie, prescribing glasses with prism strength customized to the patient’s needs to shift images and ease near-task eye coordination) can help but may be complicated by symptom fluctuation. Whereas convergence ability improves with dopaminergic therapy, it remains substantially impaired even during the “On” state.⁸ People with PD tend to have lower scores on the 25-item National Eye Institute Visual Function Questionnaire, with near-vision tasks showing particular impairment.⁸ Management of convergence insufficiency in PD includes single-vision reading glasses with base-in prism, or monocular occlusion in select cases. Multifocal or progressive lenses are discouraged, as they may hinder binocular vision and limit effective prism use in the lower portion of these lenses.

Decreased Blink Rate and Dry Eyes
Dry eyes affect ~60% of people with PD.⁹ People with dry eyes experience a sensation of ocular dryness, foreign body sensation, irritation, and blurred vision. The case of dry eyes in individuals with PD is multifactorial. Compared with healthy controls, people with PD have significantly reduced blink rates, resulting in reduced tear break-up time and decreased tear volume.¹⁰ Blink duration, possibly driven by the cholinergic system involved in inhibitory control, is prolonged in people with PD, which worsens as the disease progresses.¹⁰ Autonomic dysfunction, another hallmark of PD, also contributes to decreased tear production.

Evaluations for dry eyes include the Schirmer test and corneal fluorescein staining.¹¹ Anterior segment optical coherence tomography can also reveal corneal epithelial damage and thinning.¹²

Dry eye treatment focuses on symptom relief. Artificial tears are used every 3 to 4 hours, with preservative-free formulations recommended for more frequent use to reduce the risk of ocular surface irritation. Nighttime artificial tear gels or ointments may be applied for prolonged relief. For moderate to severe cases, cyclosporine eyedrops may reduce ocular surface inflammation and improve tear film stability. It is also important to educate patients about factors that can help to reduce dry eyes, such as avoiding irritants, minimizing screen time, avoiding smoking, and eliminating medications that may worsen dry eye symptoms.

Apraxia of Eyelid Opening
Apraxia of eyelid opening is a nonparalytic inability to voluntarily elevate the upper eyelid despite normal muscle strength and structure. Its frequent co-occurrence with blepharospasm and the shared treatment responses of apraxia and blepharospasm suggest a shared pathophysiologic mechanism between these disorders.^13,14 Apraxia of eyelid opening likely arises from dysfunction of neural circuits responsible for initiating voluntary eyelid movement, particularly the basal ganglia and frontal cortical pathways. Inhibited relaxation of the orbicularis oculi muscle may prevent effective eyelid elevation. Abnormal dopaminergic transmission, impaired blink reflex modulation, and disrupted reciprocal innervation between eyelid muscles are also implicated.¹⁴

Botulinum toxin injection into the orbicularis oculi muscle is the primary treatment for apraxia of eyelid opening and can improve eyelid function significantly.¹⁵ Case reports have reported potential benefit from aripiprazole treatment, although more research is needed to confirm its safety and efficacy.¹⁶

Visual Hallucinations
Visual hallucinations (ie, false perceptions in the absence of external stimuli) in PD may be well-formed or minor hallucinations. Minor hallucinations, which include presence hallucinations (the perception that someone is nearby when no one is present), passage hallucinations (fleeting peripheral images, often of animals or people), and visual illusions (misinterpretations of actual visual stimuli), are more commonly seen in people with PD. Visual illusions include kinetopsia (perceiving stationary objects as moving) and object misidentification (visually mistaking one object for another).¹⁷

The pathophysiology of visual hallucinations in PD involves dopaminergic and cholinergic dysfunction, visual processing deficits, and cognitive impairment.¹⁷ Minor visual hallucinations can occur in people with PD who are not taking dopamine medications, which suggests they are an intrinsic feature of PD.

Acute visual hallucinations should prompt evaluation for infection, dehydration, metabolic disturbance, or medication adverse effects. If persistent, nonpharmacologic interventions—such as optimizing the environment, minimizing sensory overload, and implementing delirium precautions—should be tried before pharmacologic treatments.

Pimavanserin (Nuplazid; Acadia Pharmaceuticals Inc., San Diego, CA), a selective 5-HT2A receptor inverse agonist without any dopamine D2 receptor antagonist properties, is the only FDA-approved medication for PD psychosis, and does not worsen motor symptoms.¹⁸ Clozapine is highly effective but requires blood monitoring due to the risk of agranulocytosis. Quetiapine is safer, but less effective. Rivastigmine, a cholinesterase inhibitor, may help in individuals with concurrent cognitive impairment.

All antipsychotics carry a black-box warning for increased mortality in individuals with dementia-related psychosis. As such, treatment with antipsychotics should be assessed on a case-by-case basis according to the risks and benefits.¹⁹

Retinal Changes
The retina and optic nerve are extensions of the central nervous system and may mirror neurodegenerative changes seen in PD.²⁰ These changes may reflect central neurodegeneration. Retinal involvement in PD is linked to dopaminergic neuron loss and α-synuclein accumulation in the retina.^21,22

Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging modality that enables detailed retinal evaluation. It holds potential not only for detecting retinal changes in PD but also for tracking disease progression and correlating retinal biomarkers with cognitive decline.²⁰ Subclinical retinal changes may occur early in the disease, suggesting OCT could aid in early diagnosis and may be used as a biomarker for PD.^20,23

Although retinal nerve fiber layer thinning has shown potential as a PD biomarker, inconsistencies remain regarding its validity, likely due to study variability. More longitudinal investigations are needed to validate retinal imaging as a reliable PD biomarker in PD. Nonetheless, the retina offers a unique, promising, and accessible window into studying central neurodegeneration.²³

Ocular Side Effects of DBS in PD
DBS is a well-established, effective treatment for refractory PD motor symptoms. Common DBS targets include the subthalamic nucleus (STN), globus pallidus internus, and, less frequently, the ventral intermediate nucleus of the thalamus. 

Ocular side effects, particularly involving abnormal eye movements, are reported following DBS, particularly with STN and ventral intermediate nucleus of the thalamus targeting.²⁴ Axonal fibers from the frontal eye fields course laterally to the STN within the internal capsule. Stimulation spread resulting from DBS can activate these fibers, leading to contralateral conjugate gaze deviation. Medial STN stimulation may involve oculomotor nerve fascicles, resulting in ipsilateral gaze deviation.²⁵ Other ocular complications associated with DBS include blepharospasm, apraxia of eyelid opening, and diplopia. Careful programming and electrode placement are essential to minimize unintended stimulation of nearby oculomotor pathways while preserving therapeutic motor benefits. 

Conclusion
Nonmotor neuro-ophthalmologic manifestations of PD are common and can greatly affect QoL in people with PD. These symptoms, ranging from dry eyes, to double vision, to visual hallucinations, may occur at various disease stages. Some symptoms are worsened by treatment (eg, visual hallucinations from dopaminergic therapy); others (eg, dry eyes) appear early. Treatment-related effects, such as those from DBS, can contribute to ocular complications.

Advancements in diagnostic tools, such as OCT and eye-tracking technology, have enhanced our ability to detect subtle ocular abnormalities, which may serve as future PD biomarkers. However, further research is needed to validate and incorporate these findings into clinical practice. Recognizing and addressing neuro-ophthalmologic signs and symptoms is essential for delivering comprehensive, patient-centered care and improving long-term outcomes in individuals with PD.