Research Finds Protein Link to Post-Surgery Eye Pain

Oregon Health & Science University
Findings could lead to new screening tools, treatments for pain after surgeries such as LASIK

A patient's eyes and tears are tested in a cornea exam room in the Casey Eye Institute on Fri., July 12, 2024. OHSU researchers have discovered differences in tear proteins between people who experience pain after refractive surgery and those who don't. (OHSU/Christine Torres Hicks)

A patient's eyes and tears are tested in a cornea exam room in the Casey Eye Institute on Fri., July 12, 2024. OHSU researchers have discovered differences in tear proteins between people who experience pain after refractive surgery and those who don't. (OHSU/Christine Torres Hicks)

Each year, more than 800,000 Americans undergo refractive surgery like LASIK and PRK to correct their vision. While these procedures generally have a high rate of success, a small number of people continue to feel pain or discomfort long after the surgery.

In a new study published in the Journal of Proteome Research, Oregon Health & Science University researchers discovered a connection between levels of certain proteins found in patients' tears and persistent pain months after surgery. The team hopes their findings could eventually help in the development of new screening tools and treatments for patients.

Sue Aicher, Ph.D., has short gray hair, a blue top, and smiling in a garden near Casey Eye Institute.

Sue Aicher, Ph.D. (OHSU)

"A lot of people think tears are just salt water, when in fact we are able to detect thousands of proteins in human tears," said Sue Aicher, Ph.D., corresponding author on the study and a professor of chemical physiology and biochemistry in the OHSU School of Medicine who studies how cells function in neural circuits, particularly in pain.

"It is such a rich proteome, and those proteins may impact the activity of nerves at the surface of the eye in the cornea."

Revealing protein patterns

The team recruited 120 study participants in Miami and Portland. None reported any eye pain before refractive surgery.

Three months after surgery, researchers took tear samples using a thin filter paper inserted beneath the lower eyelid to wick tears from the eye surface. This non-invasive procedure is used clinically for other diagnoses, such as assessing dry eye disease.

From the group of participants, 16 reported they still had pain. Researchers compared these participants' tears with those of the 104 participants who had no pain and identified 2,748 proteins in tears from both groups of participants.

When they compared protein profiles among the two groups, they found that some proteins differed in people who experienced long-term pain compared with those who did not. Additionally, researchers found patterns of protein differences mattered: Looking at three or four proteins together was better at predicting pain than a single protein.

Brooke Harkness, O.D., has long auburn hair, a blue top, smiling in a garden near Casey Eye Insitute.

Brooke Harkness, O.D. (OHSU)

The study's lead author, Brooke Harkness, O.D., M.S., FAAO, assistant professor of ophthalmology at OHSU Casey Eye Institute, works with patients who have severely dry eyes, corneal pain and other ocular surface diseases.

"Many of these differential proteins are involved in pathways of the immune system, inflammation and damage to the corneal nerves," she said. "So, it's not a random mix of proteins, but a pattern that we're seeing. I think that's pretty exciting."

The bioinformatics team, led by Jodi Lapidus, Ph.D., and Siting Chen, M.P.H., of the OHSU-PSU School of Public Health, used statistical tools to test if specific proteins or groups of proteins could predict whether eye-surgery patients would have long-term pain. Researchers say these protein patterns might one day help assess the risk of post-surgical eye pain in patients.

"These refractive surgeries are typically elective," Harkness said. "If you can give people information about their individual risk level for developing persistent pain after surgery, they can make a careful decision about whether they want to proceed."

The team also said their findings could lead to new therapies for treating eye pain.

"We hope to eventually develop drug treatments that modulate the proteins that are elevated, and see if that can treat the eye pain," Aicher said.

Other contributors to this study include OHSU researchers Kilsun Kim, M.S., Ashok Reddy, Ph.D., Trevor McFarland, B.S., Deborah Hegarty, Ph.D., Steven Everist, B.S., Julie Saugstad, Ph.D.; and, Anat Galor, M.D., M.S.P.H., of the University of Miami Health System's Bascom Palmer Eye Institute.

This study was supported by the National Institutes of Health's National Eye Institute award R61EY032468. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH/NEI.

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