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:
- Tear film
- Inflammation
- Meibomian glands
- Eyelids/lid margin disease
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.
