Evaluation of Tear Protein Markers in Dry Eye Disease with Different Lymphotoxin-Alpha Expression Levels

Purpose: To compare tear protein markers between normal subjects and patients with dry eye (DE) and high and low lymphotoxin-alpha (LT-α) levels.

Design: Prospective cross-sectional study.

Methods: Patients with DE were divided into low (≤700 pg/mL) and high (>700 pg/mL) LT-α groups. Twelve protein markers were measured by microsphere-based immunoassay and ocular surface parameters were determined in right eyes (33 high LT-α DE, 27 low LT-α DE, and 20 control eyes) and left eyes (21 high LT-α DE, 39 low LT-α DE, and 20 control eyes).

Results: In both eyes, tumor necrosis factor-α (TNF-α), interleukin (IL)-10, IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-17A, and IL-12/23 p40 levels in high LT-α DE were significantly higher (P < .01) than in low LT-α DE. Significant correlations identified in high LT-α DE were: Standard Patient Evaluation Eye Dryness with IL-10 (R = 0.43, P = .013), IL-1β (R = 0.48, P = .005), and IL-12/23 p40 (R = 0.50, P = .003), IL-12/23 p40 with ocular surface disease index (R = 0.35, P = .049), and epidermal growth factor with corneal fluorescein staining score (R = -0.36, P = .038). Significant correlations in low LT-α DE were: Standard Patient Evaluation Eye Dryness with IL-10 (R = -0.39, P = .046), TNF-α (R = -0.39, P = .047), and IL-17A (R = -0.48, P = .013), ocular surface disease index with TNF-α (R = -0.47, P = .017) and IL-17A (R = -0.46, P = .018), and IL-6 with tear breakup time (R = -0.40, P = .044). Lastly, IL-1Ra levels significantly increased in DE patients, positively correlated with temporal conjunctival hyperemia index, and negatively correlated with Schirmer I test (P < .05).

Conclusions: Our study identified tear IL-1Ra level as a potential biomarker to replace the Schirmer I test. Multiple tear protein marker levels increased in high LT-α DE, indicating that high LT-α DE might have a different pathogenesis.