Spatial Distribution of Noninvasive Break Up Times and Clinical Relevance in Healthy Participants and Mild Dry Eye

Purpose: Noninvasive keratograph break up times (NIKBUTs) are preferred to dye-based methods to evaluate tear stability in translational medicine. We analyzed the NIKBUTs in different regions of the precorneal tear by using a common imaging technology and explored potential correlations with clinical parameters. Methods: We tested NIKBUTs of 120 participants (62.5% females, aged 61.0 +/- 13.8 years) with the Keratograph 5M, with standardized symptoms, ocular surface evaluation, and tear lipid layer interferometry. NIKBUTs were obtained from color maps in up to 165 spatial zones corresponding to 7 concentric rings. Results: The lowest NIKBUT of tested zones averaged 7.8 +/- 7.4 seconds (median, 4.5; range, 1.5-24 seconds), with the lowest NIKBUT measuring <2 seconds in many inferior zones. A mean of 5 zones had broken up by 2 seconds compared to a mean of about 50 zones by 10 seconds. NIKBUTs in specific inferior peripheral zones were significantly directly correlated to tear lipid thicknesses. The receiver operating characteristics for detecting reduced tear lipid thickness were better than overall NIKBUTs for participants with readings in these zones. Weaker correlations of NIKBUTs with symptoms were observed in two other zones. Overall, the NIKBUT displayed by keratograph was not significantly associated with any clinical parameters. Conclusions: Decreased NIKBUTs in specific peripheral locations may be associated with lower lipid thicknesses. Future measurements of NIKBUTs should ideally be determined in smaller defined zones than current maps. Translational Relevance: An understanding of how to evaluate tear stability allows a more robust clinical evaluation of new drugs and medical devices for dry eye.