Subclinical keratoconus and inflammatory molecules from tears

TLDR

Keratoconus is characterized by corneal thinning driven by inflammatory mediator expression. The study aimed to quantify proinflammatory cytokines and MMP‑9 in tears from both eyes of unilateral keratoconus patients. Tear samples from 30 asymmetrical keratoconus patients and 20 controls were collected and analyzed by ELISA for IL‑6, TNF‑α, and MMP‑9. IL‑6 and TNF‑α were elevated in both KC and subclinical KC tears compared with controls, while MMP‑9 was markedly increased only in KC eyes, indicating chronic inflammation contributes to keratoconus pathogenesis.

Abstract

Tissue degradation in corneal thinning disorders, such as keratoconus (KC), involves the expression of inflammatory mediators. The purpose of this study was to determine the levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP-9) in tears from both eyes of unilateral keratoconus (KC) patients.Thirty patients diagnosed as having asymmetrical KC (30 KC eyes, and 30 subclinical KC eyes) and 20 normal control subjects (one eye) were studied in a prospective, cross-sectional study. Keratoconus screening programmes were performed on these participants. Ten microlitres of tears was collected from each eye. The concentrations of cytokines (interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha)) and MMP-9 were measured by ELISA.Mean values for IL-6 levels were similar in KC and subclinical KC samples (5.5 (4.9 to 6.9) vs 5.7 (4.5 to 6.2) pg/ml, p = 0.131), but significantly higher in relation to the control group (2.2 (1.0 to 4.1) pg/ml, p<0.0001). Significant differences were found in TNF-alpha levels between KC and subclinical KC eyes (5.4 (4.1 to 6.8) vs 4.8 (4.2 to 6.0) pg/ml, p = 0.032) and control group (1.8 (1.5 to 2.3) pg/ml, p<0.0001). Increased values of MMP-9 were found in KC (59.4 (50.6 to 66.1) ng/ml) vs subclinical KC eye (7.0 (4.8 to 8.6) ng/ml) (p<0.0001). MMP-9 levels in the control group (6.1 (3.9 to 8.3) ng/ml) and subclinical KC were similar (p = 0.203).IL-6 and TNF-alpha are overexpressed in the tears of subclinical and KC eyes. Increased MMP-9 levels were found only in the KC eye. These results indicate that the pathogenesis of KC may involve chronic inflammatory events.