Parkinson's Disease and the Eye: What You Need to Know

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder.¹ With 90,000 new diagnoses every year in the US, people living with the disease will reach a 1.2 million all-time high by 2030.²

Life expectancy is largely unaffected by PD,³ meaning that most patients live with it, rather than die from it. Eyecare providers (ECPs) have the unique opportunity to significantly improve patient’s quality of life by directly addressing visual manifestations and strengthening treatment efficacy by monitoring disease progression through customized exams and initiating interdisciplinary care.

A brief overview of Parkinson’s disease

PD is a progressive disease that directly affects movement, mood, behavior, and sleep. It impacts cognition, impulse control, working memory, learning, attention, motivation, and dreaming. Dopamine is found in the olfactory bulb, midbrain substantia nigra, hypothalamus, ventral tegmental area (VTA), retina, and the periaqueductal gray area and contributes to various body functions and behaviors.⁴

PD is caused by decreased dopamine production in the brain. In addition, the inhibition of prolactin production is a byproduct of the condition. People with Parkinson’s (PwP) do not experience symptoms until approximately 60 to 80% of the dopamine-producing neurons are lost in the VTA of the substantia nigra.^4,5

As represented in Table 1 below, dopamine depletion in PD leads to specific motor and non-motor symptoms.⁶

Motor Symptoms	Non-motor Symptoms
Resting tremor	Constipation
Bradykinesia	Hyposomia
Rigidity	Rapid eye movement (REM) sleep behavior disorder
Postural instability	Mood disorders
	Urinary frequency/urgency

^{Table 1: Courtesy of Johns Hopkins Medicine.}

Understanding PD and the visual system

PD can affect multiple aspects of the visual system, but these symptoms are often not readily disclosed by patients and overlooked by healthcare providers.^6,7 In one cross-sectional study, 82% of PwP reported one or more ophthalmic symptoms, and 68% revealed they impaired daily activities.¹¹

Below are potential ocular complications of PD and clinical pearls to serve these patients best:

Blinking/lid abnormalities
- Blepharitis: Associated with low blink rate and unstable tear film
- Blepharospasm
- Ocular apraxia: Inability to voluntarily open their eyes, often while speaking
Blurred vision
- Multifactorial—PD-related causes may include:
  - Eye movement problems
  - Anticholinergic medications
Color and contrast vision problems
- Affects 18 to 50% PwP
- Due to the depletion of dopamine levels in the retina
Diplopia
- Affects approximately 10 to 30% PwP and is multifactorial
  - Monocular diplopia: Age-related cataracts or dry eye
  - Binocular diplopia: Binocular disorders or new onset strabismus
  - Selective diplopia: Rare type of Parkinsonian hallucination
Dry eye
- Affects approximately 60% PwP
- Due to blink rates as low as 1 to 2 times/min
- Related to depleted dopamine levels and associated medications
Eye movement problems
- Saccadic dysfunction
- Vergence disorders
Palinopsia
- Long-lasting high-resolution after-images¹³
- Can be seen minutes, days, or weeks after the original image is seen¹³
Spatial awareness
- Changes in visual processing
- Caused by reduced volume of gray matter in visual centers of the brain
Visual hallucinations
- Affect 75% PwP as the condition progresses

A specialized approach to Parkinson’s disease patients

Customized eye exams for PwP not only evaluate for all ocular diseases (cataracts, glaucoma, retinal abnormalities, etc), but target specific patient needs.

ECPs can easily incorporate tests into their current pretesting and exam routine to identify, monitor, and proactively manage the underlying causes of PD-related ocular symptoms.

PD eye exam protocol:

Have patients fill out the Visual Impairment in Parkinson’s Disease Questionnaire (VIPD-Q) prior to the exam or with the technician during pretesting. These answers can be used to guide patient history and as a jumping-off point for further discussion.
Include distance and near contrast sensitivity testing in pretesting with the technician (e.g., Mars Letter Contrast Sensitivity Test for distance and Lea Numbers Low-Contrast Flip Chart for near).
Administer color vision testing focusing on blue-yellow abnormalities (e.g., Hardy Rand Rittler [HRR] test).
Perform ocular motility testing, such as vergences, saccades, phorias, and near point of convergence (NPC).
Evaluate the cornea with sodium fluorescein (NAFL) and tear breakup time (TBUT).
Attain anterior segment and retinal photos to monitor changes.
Perform optical coherence tomography (OCT) and OCT angiography (OCTA) to monitor for retinal thinning, as OCT imaging has shown promise in monitoring disease progression,¹⁰ and combined OCT/OCTA testing has shown improved diagnostic value when compared to either OCT or OCTA alone.¹²

Key features of PD in OCT/OCTA testing

A 2020 study found reduced temporal retinal nerve fiber layer (RNFL) thickness, total macular volume (TMV), macular retinal thickness (MRT), and ganglion cell-inner plexiform layer complex (GCL-IPL) thickness via spectral-domain OCT (SD-OCT) testing.¹²

The same study revealed significantly lower vessel length density (VLD) at the central (1mm diameter around fovea), inner (1 to 3mm diameter around fovea), and full (6mm diameter from the fovea) regions via SD-OCTA.¹²

Additionally, vessel perfusion density (VPD) in all regions (1mm, 1 to 3mm, 3 to 6mm and 6mm diameter around fovea), and foveal avascular zone (FAZ) circularity index were also significantly lower in PwP when compared to study controls.¹²

While further studies are needed, these noninvasive procedures will likely become an integral part of PwP care.

Parkinson’s ocular management

Many of the PD-related ocular complications can be treated effectively in a primary eyecare office, while others, including those unresponsive to treatment, will require a referral to the treating neurologist, neuro-ophthalmologist, or other specialist.^6,7,9,10

Below are ocular conditions associated with PD and steps for managing the symptoms:

Vergence disorder
- Prisms for near and/or vision therapy
- Separate glasses for distance and near
- Consult the treating neurologist to optimize the levodopa regimen
Blepharitis
- Educate patient and monitor
- Warm compresses
- Lid scrubs
- Medicated ointment
Color vision deficiency
- Educate patient and monitor pro re neta (prn)
- Consult the treating neurologist to evaluate the medication regimen, some medications may improve symptoms
Visual hallucinations
- Coordinate care with neurologist
- Lowering peak levodopa levels may help¹⁰
- Cholinesterase inhibitors or antipsychotics may help¹⁰
Medication-induced blur
- Anticholinergics such as trihexyphenidyl (Artane) or benzotropine (Cogentin) can cause dryness and pupil dilation/ciliary relaxation, resulting in blurred vision⁷
- Educate patient and monitor prn
- Blur may subside with use
- Coordinate care with the treating neurologist
Dry eye
- Artificial tears four to six times/day, monitor
- Consider tear duct occlusion
- Consult with the neurologist and consider levodopa and carbidopa at the same time
Decreased contrast sensitivity
- Educate the patient on decreased night vision and difficulty with text on a colored background
- Monitor prn
Reduced spatial awareness
- Educate and suggest adequate lighting
- Visual cues, such as a portable laser device, may help
- Monitor prn
Blepharospasm/Ocular apraxia
- Educate patient
- Rubbing may help mild cases
- Lid crutches
- Botox injections
Palinopsia
- Educate patient and monitor prn
- Coordinate care with a neurologist
- May need increased frequency or dosage of levodopa

Recent developments in research on PD

A new cross-sectional data analysis investigated potential retinal biomarkers using fovea-centered OCT scans to evaluate the macular RNFL (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses.¹⁴

The analysis used data from the AlzEye study, a retrospective study with a cohort of 154,830 patients, 700 with PD, and the UK Biobank (UKBB) study, a prospective population-based cohort of 67,311 patients, 54 of which developed PD.¹⁴

The AlzEye cohort revealed PwP had thinner parafoveal GCIPL compared to controls (all inner subfields: -2.12μm, 95% confidence interval [CI]: -3.17 to -1.07, p=8.2×10^-5) and most notable inferiorly (-2.38μm, 95% CI: -3.54 to -1.22, p=6.0×10^-5).¹⁴ This trend was also observed for INL (all inner subfields: -0.99μm, 95% CI: -1.52 to -0.47, p=2.1×10^-4) and was most prominent superiorly (-1.09μm, 95% CI: -1.70 to -0.47, p=5.9×10^-4).¹⁴

The UKBB study revealed that patients with thinner GCIPL (hazards ratio [HR]=0.62, 95% CI: 0.46 to 0.84 per SD increase, p=0.002) and INL, particularly inferiorly (HR=0.66, 95% CI: 0.51 to 0.86, p=0.002), were more likely to develop PD.¹⁴ In addition, the study suggests that thinner ganglion cell complexes may correlate to the degree of dopaminergic degeneration and potential conversion to Lewy body disease.

While more studies are needed to determine specific clinical implications and protocols, OCT imaging is a non-invasive procedure that could play a vital role in diagnosing PD several years before clinical presentation and can potentially provide a better understanding of individual prognosis, disease progression, and treatment efficacy.

Conclusion

Specialized eye exams, enhanced patient engagement, and personalized multi-disciplinary care are imperative to the successful ocular management of PwP.

Primary eyecare providers can substantially improve the quality of life by maximizing patient independence and playing a vital role in delivering the best care possible for these patients.