Chronic Ocular Pain Development Linked With Increased Interleukin-9 Tear Levels

Young girl with tears in eyes
Young girl with brown eyes with tear falling.
Understanding the role of tear cytokines and neuromodulators as biomarkers of chronic ocular pain may assist clinicians with treatment strategies.

Chronic ocular pain development may be associated with higher interleukin-9 (IL-9) tear levels, according to a study published in Experimental Eye Research. Additionally, nerve growth factor (NGF) appears to be associated with ocular pain and dry eye (DE) in patients who underwent refractive surgery (RS).

Researchers conducted a study to determine which tear cytokines and related molecules are associated with chronic ocular pain involved in DE and RS.

They performed a tear concentration analysis on 180 patients (mean age 51.0±14.7 years, 118 women) and divided them into 5 groups: patients with DE and chronic ocular pain following RS (group 1, 28.9%), patients without DE and chronic ocular pain following RS (group 2, 16.7%), patients with DE and chronic ocular pain without RS (group 3, 17.2%), patients with DE without pain or previous RS (group 4, 19.4%), and patients without ocular symptoms or previous ocular surgeries (control group, 17.8%). Participants who underwent RS had laser-assisted in situ keratomileusis (LASIK) at least 3 months before.

Group 3 was predominantly composed of women (87.1%), group 1 members were the youngest (aged 34.8-39.4 years), and group 4 was the oldest (aged 58.9-66.9 years).

The team evaluated patients after allowing them 30 minutes to adapt to a normal controlled environment. They then performed clinical exams and collected tear samples. Researchers measured  tear concentrations of 20 cytokines with immunobead-based assay and measured substance P (SP) tear levels with enzyme-linked immunosorbent assay (ELISA).

The investigators noted that chronic ocular pain was linked with higher IL-9 tear levels, while IL-10, SP, macrophage inflammatory protein (MIP)-1ɑ/CCL3, IL-2, and interferon (IFN)-ɣ were linked with prior RS. IL-8/CXCL8, MIP-1ɑ/CCL3, IL-2, and IFN- ɣ were linked with DE-related inflammation. NGF was associated with chronic ocular pain and DE in RS patients.

“Improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions,” according to the researchers.

Limitations of the study include the exclusion of patients with surgeries other than LASIK, a failure to differentiate between different types of ocular pain, and failure to consider intensity of pain in DE patients without RS.


Blanco-Vázquez M, Vázquez A, Fernández I, et al. Inflammation-related molecules in tears of patients with chronic ocular pain and dry eye disease. Exp Eye Res. Published online March 29, 2022. doi:10.1016/j.exer.2022.109057