Sarah Hamm-Alvarez, PhD: Comparing Basal & Reflex Tears

Currently, Parkinson disease is typically diagnosed when the typical symptoms of motor dysfunction appear. However, at that point, irreversible damage to neurons has already occurred.

This spurred investigators at the USC Roski Eye Institute to look for a biomarker that would allow for earlier detection and diagnosis of Parkinson disease. To do this, they turned to tears.

Sarah Hamm-Alvarez, PhD, Professor of Ophthalmology at the USC Roski Eye Institute at the Keck School of Medicine of USC, spoke with MD Magazine® about this biomarker research, which she presented at the 2019 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Vancouver, BC.

When they compared tears from patients with Parkinson to healthy controls, the investigators found “fairly significant changes in a protein called oligomeric α-synuclein,” said Hamm-Alvarez. That protein is connected to the Lewy bodies that are characteristic of Parkinson disease, she added.

In part 1 of the interview, Hamm-Alvarez introduced the study and the team’s reasons for investigating tears for a Parkinson biomarker.

What were the study methods?

When we started this study, we recruited patients who were diagnosed with Parkinson's disease already, as well as healthy control subjects. These healthy control subjects were either the caregivers who accompanied the patients to the clinic or were other medical staff at the USC hospital and the movement disorders clinic.

What differences did you find between Parkinson patients' tears and control tears?

How did basal tears and reflex tears compare?

We collected their tears with something called a Schirmer's test strip, which is a strip that's clinically used to measure tear flow. So, it's a little piece of filter paper that's placed on top of the lower eyelid and over a period of 5 minutes it wicks the tears onto the strip. It's a very non-invasive test which is important because these patients experience a lot of tremor and we don't want to put anything sharp next to someone's eye who is experiencing tremor. And then we take the strip away and elute the proteins and we measure what changes in a certain spectrum of proteins occurred.What we found were that there were fairly significant changes in a protein called oligomeric α-synuclein. So, oligomeric α-synuclein is an intermediate in the formation of something called the Lewy body. So, when patients are diagnosed with Parkinson's disease, one of the characteristic pathological features is the Lewy body formation, which is found in the brains of patients with Parkinson's disease. This is found actually on autopsy, so it's not something that can be diagnosed in in real time.We did actually measure both what we call basal tears—which is in the absence of any stimulation—these are tears that are taken under topical anesthesia with an eye drop, and then we also measured without anesthesia—which does involve a little bit of reflex stimulation of the cornea, which is really just the touching of the Schirmer strip to the cornea. Interestingly we found that the levels of oligomeric α-synuclein and the difference between the healthy controls and the Parkinson's disease patients were higher in those reflex tears, which engage the nerves to a greater degree.