Eyes’ Pupils May Be Window Into Assessing Disease Stage

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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A person with several eyeglasses near his hand, holds the other hand over one eye while a vision chart is seen in the background.

The response of the eyes’ pupils — the black circle in the center of the eye  that allows light to enter — seems to change according to the progression of Parkinson’s disease, a recent study has found.

The results suggest that measuring the pupils’ response to stimuli could become a noninvasive way to measure disease progression.

The study, “Analysis of pupillometer results according to disease stage in patients with Parkinson’s disease,” was published in Nature: Scientific Reports.

The pupil is the hole situated in the center of the iris (the colored part of the eye) that allows light to enter the retina, a lining of tissue at the back of the eye that is sensitive to light.

The iris is a contractile structure, and expands or dilates depending on the amount of light available. In this way it regulates the amount of light by controlling the size of the pupil, functioning like a photography camera’s aperture. This movement is known as the pupil light reflex (PLR) and plays a key role in determining the eye’s image quality and response to light.

A team of researchers in South Korea looked at the PLR using a pupillometer, an instrument used to measure pupil response to light. This reflex allows one to assess the functionality of the autonomic nervous system — the part of the body that controls involuntary actions such as digestion and heartbeat — and is known to be dysfunctional in certain Parkinson’s patients.

Measuring the PLR is noninvasive and helps researchers determine the balance of the parasympathetic and sympathetic systems, two opposite parts of the body’s autonomic nervous system.

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The sympathetic system activates several bodily functions when an imminent threat or major stressor is perceived, while the parasympathetic system works to calm the body afterward. Measuring the balance between these two systems can be a useful test for patients with neurological disorders.

In this study, patients with Parkinson’s were divided into early or late stages based on the Hoehn and Yahr scale (HY scale). Among the 132 patients, 100 were early stage (HY stages 1–2) and 32 were late stage (HY stages 3–5). After matching both groups for age and sex (to compensate for the effect of age on pupil light reflex), only 64 patients remained in the early stage group.

Those with late stage disease had longer disease duration and higher levodopa equivalent daily doses, meaning they were on higher doses of medications to treat their disease.

The study found there was a significant difference between the two groups in terms of pupil constriction velocity (the speed at which the pupil contracts when exposed to light) and maximum constriction velocity, which were significantly slower in the late-stage group.

“Constriction velocity and maximum constriction velocity are parameters involving the parasympathetic system, and changes in these parameters suggest that in patients with PD [Parkinson’s disease], the abnormalities of the PLR are mainly caused by parasympathetic autonomic dysfunction,” the researchers wrote.

There was not a significant difference in the two groups when it came to pupil dilation velocity (how quickly the pupil dilates when light is removed), baseline pupil size, minimum pupil diameter, and constriction latency, the delay in pupil constriction following light stimulation — all parameters that involve the sympathetic system.

The researchers noted that pupillary dilation response may have not been affected because the medications that the patients were taking may have affected the sympathetic nervous system, and thus offset the progression of the disease on dilation response.

“[T]he parameters measured by pupillometry changed according to the motor progression of PD,” the researchers wrote, adding that “pupillary parasympathetic dysfunction progresses with the progression of PD. In contrast, the factors related to sympathetic dysfunction did not change much, implying that pupillary sympathetic dysfunction advances relatively slowly even [in] PD advanced.”

The authors thus suggest the progression of Parkinson’s disease could be identified measuring pupil constriction velocity.