Published in Ocular Surface

Understanding New Research on Cytokine Levels in Tears of Dry Eye Patients

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6 min read

Join Damon Dierker, OD, FAAO, and Nathan Lighthizer, OD, FAAO, to review the findings from a study on cytokine levels in the tears of dry eye patients.

In the fourth installment of the Dry Eye Fireside Chat series, Damon Dierker, OD, FAAO, sits down with Nate Lighthizer, OD, FAAO, to discuss a new study on cytokine levels in the tears of dry eye patients.

What are cytokines?

Inflammation plays an integral role in dry eye disease (DED), whether it be evaporative or aqueous deficient dry eye. As such, cytokines (i.e., interleukins [IL], interferons, tumor necrosis factors [TNF], etc.) are involved in DED as well because these substances are secreted by a variety of cells throughout the body to help regulate immune function, explained Dr. Lighthizer.
While cytokines are critical for fighting off pathogens, an excess of them can also result in inflammation that leads to chronic conditions, such as DED. Dr. Dierker added that he considers acute episodes of dry eye to be a “cytokine storm” on the ocular surface, as there is a release of cytokines on the surface that cause localized damage, initiating a vicious cycle of inflammation known as chronic DED.

A recent study on cytokines in dry eye patient tears

Last year, the study “Pro- and Anti-Inflammatory Cytokine Levels in Tears of Dry Eye Subjects” was presented at the World Cornea Congress. The study looked at the levels of nine different cytokines in the tears of 30 healthy patients and 30 dry eye patients. Patients in the dry eye cohort were required to have an eye dryness score >60 and a Schirmer’s test score of <5 in one eye and <10 in the other.
To measure the cytokine levels, the research team used Schirmer’s strips to capture the cytokines and then sent the strips to a lab to perform assays. Of the nine different cytokines tracked in the study, seven were pro-inflammatory, and two were anti-inflammatory cytokines (IL-4 and IL-10).
As a side note, Dr. Lighthizer advised ECPs to keep in mind that not all cytokines are pro-inflammatory, and in a healthy ocular surface, anti-inflammatory cytokines help to regulate inflammation and balance anti-inflammatory ones.
The research team found that the dry eye patients had a presence of all the cytokines—both pro- and anti-inflammatory—and cytokine levels were statistically significantly elevated in the dry eye cohort compared to the control group.

They found a direct relationship between cytokine levels and eye dryness; when cytokine levels increased, so did the eye dryness scores, while the Schirmer’s test scores decreased.

What can clinicians take away from this study?

Dr. Dierker commented that he—and many other American optometrists—don’t routinely use Schirmer’s strips in clinical practice, so he wondered what this study could offer clinicians.
Dr. Lighthizer responded that the key takeaway of this study is that DED is linked with elevated inflammatory markers (i.e., cytokines). So, when treating dry eye patients, it is helpful to maintain an internal checklist of specific factors that need to be addressed in order to treat the condition holistically.
Elements to address when treating dry eye patients include:
Further, this study highlights that inflammation needs to be addressed in dry eye patients in order to provide them with lasting symptom relief. Additionally, treating inflammation quickly is crucial to prevent the cycle of inflammation from starting and worsening the condition of the patient’s ocular surface.
Luckily, eyecare practitioners (ECPs) have a variety of options available to address inflammation, such as topical steroids, immunomodulators, and other interventions that stabilize the tear film.

Natural tear production and inflammation

Next, Dr. Dierker asked for further clarification on whether increasing natural tear production decreases inflammation and dry eye symptoms. In response, Dr. Lighthizer explained that anytime tear production can be stimulated naturally, that will optimally provide the patient with a healthier ocular surface.
He added that there is more than just meibum, lipids, and aqueous in tears; there are hundreds of substances in tears that cannot be replicated in artificial tears. So, increasing natural tear production is beneficial for reducing inflammation due to the nutrients in tears.
Dr. Lighthizer compared artificial tears to watering plants in that watering plants with a watering can is helpful for maintenance, but because rain has natural nutrients that can nourish plants, it is the best form of hydration for plant life.

Treatments for stimulating natural tear production

Similarly, one of the best approaches to treating DED is enhancing and improving the aqueous, meibum, and mucin layers of the tear film by stimulating natural tear production.
As such, an additional approach for increasing natural tear production includes Tyrvaya (varenicline solution nasal spray 0.03mg, Viatris), a nasal spray that enhances all three layers of the tear film.
He concluded that the meibomian glands and inflammation contribute to the overall well-being of the patient’s ocular surface, so it is important to target them with treatment approaches. Simultaneously, it is possible to improve the meibomian glands and reduce inflammation if all three layers of the tear film are healthy and the body is producing tears naturally, similar to a healthy patient.

Take home

As DED is a multifactorial condition, it is vital to understand the various factors that could contribute to the dysregulation of the ocular surface.
This study demonstrates that a low Schirmer’s test score indicates increased inflammation (i.e., higher levels of pro- and anti-inflammatory cytokines) and worse dry eye signs and symptoms. Consequently, Schirmer’s test strips could act as additional diagnostic tests for clinicians evaluating dry eye patients.
Damon Dierker, OD, FAAO
About Damon Dierker, OD, FAAO

Dr. Dierker is Director of Optometric Services at Eye Surgeons of Indiana, an adjunct faculty member at the Indiana University School of Optometry, and Immediate Past President of the Indiana Optometric Association. Dr. Dierker is the Co-Founder and Program Chair of Eyes On Dry Eye, the largest event for eyecare professionals in the industry. He has made significant contributions to raising awareness of dry eye and ocular surface disease in the eyecare community, including the development of Dry Eye Boot Camp and other content resources across dozens of publications.

Damon Dierker, OD, FAAO
Nathan Lighthizer, OD, FAAO
About Nathan Lighthizer, OD, FAAO

Born and raised in Bismarck, ND, Nate Lighthizer, OD, FAAO, is a graduate of Pacific University College of Optometry. Upon graduation, he completed a residency in Family Practice Optometry with an emphasis in Ocular Disease through Northeastern State University Oklahoma College of Optometry. Dr. Lighthizer has since joined the faculty at the Oklahoma College of Optometry and serves as the Chief of Specialty Care Clinics and the Chief of Electrodiagnostics Clinic.

In 2014, he founded and now heads the Dry Eye Clinic at the College of Optometry. Also in 2014, he was named the Director of Continuing Education as well as the Assistant Dean for Clinical Care Services at the Oklahoma College of Optometry. He is a founding member, and currently serves as Vice President, of the Intrepid Eye Society which is a group of emerging thought leaders in optometry. He was named a member of PCON 250—a list of the top 250 optometrists in the country who practice progressively, provide innovative patient care, conduct optometric research or excel in academia and share what they have learned with other optometrists to advance the profession.

Dr. Lighthizer lectures nationally on numerous topics, most notably advanced ophthalmic procedures, electrodiagnostics, and ocular disease.

Nathan Lighthizer, OD, FAAO
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