Tear Fluid Cytokine Analysis: A Non-Invasive Approach for Assessing Retinopathy of Prematurity Severity

Abstract

Abstract Purpose: To determine whether there is a significant association between the inflammatory cytokines in the tear fluid and the severity of the Retinopathy of Prematurity Severity (ROP). Study Design: Retrospective cohort study. Methods: The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment. Results: Significantly higher levels of CCL2 and VEGF were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics analysis. We show combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for the severe ROP (area under curve, 0.85). Conclusion: The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP.