Tear biomarkers in patients suffering from chronic pain and dry eye disease

Abstract

Purpose : To analyze the concentration of tear cytokines and substance P (SP) in patients suffering from chronic pain and/or dry eye (DE) who either had previous LASIK-type refractive surgery (RS) or did not have it.

Methods : 180 subjects were recruited and divided into 5 groups: 52 patients with pain and/or DE post-RS (P/DE-RS); 31 non-RS patients with pain and DE (P/DE-nonRS); 35 non-RS patients with only DE (DE-nonRS); 30 asymptomatic post-RS control subjects (C-RS); and 32 asymptomatic non-RS control subjects (C-nonRS). Inclusion criteria for DE were: Ocular Surface Disease Index score ≥13 and abnormal results in both eyes of at least 2 of the following tests: tear break-up time ≤7 sec, Schirmer ≤5 mm and corneal or conjunctival staining ≥1 (Oxford scale). Chronic ocular pain was considered when lasting ≥3 months and the Numerical Rating Scale score was ≥2 (range 0-10). Concentration of EGF, fractalkine, IL-1b, IL-1Ra, IL-2, IL-4, IL-6, IL-8, IL-9, IL-10, IL-17A, MCP-1, MCP-3, TNF-a, IFN-g, GRO, MIP-1a, MIP-1b, NGF and RANTES in tear samples was analyzed by multiplex immunobead-based assay and SP concentration by enzyme-linked immunosorbent assay. The relationship between markers and groups were evaluated by ANCOVA using propensity score to control age and sex effect. Molecules with percentage of detection <50% (IL-17A, IL-2, IL-9, IFN-g and MIP-1a) were analyzed using contingency tables.

Results : IL-10 tear concentration was significantly higher in the groups who had LASIK RS (P/DE-RS and C-RS) than in DE-nonRS (p<0.02) or C-nonRS (p<0.03). SP was significantly elevated in both LASIK groups (P/DE-RS and C-RS) compared to the two non-RS symptomatic groups (P/DE-nonRS and DE-nonRS) (p<0.03 and p<0.02 respectively). SP concentration was also higher in controls who had RS (C-RS) than in controls who did not have it (C-nonRS) (p=0.018). IL-9 showed the highest percentage of detection in groups with pain (P/DE-RS and P/DE-nonRS) (p=0.0001). LASIK groups followed by P/DE-nonRS group had the highest percentage of detection of MIP-1a (p=0.0003). IL-17A was only detected in the C-RS group.

Conclusions : IL-10, SP, MIP-1a and IL-9 might be involved in the development of chronic pain in patients who had RS and in DE patients. These results add further insight into the molecular mechanisms involved in the development of chronic pain and DE and might be helpful in the design of new therapeutic approaches.

This is a 2021 ARVO Annual Meeting abstract.