Evaluating Dry Eye Disease Subtypes Based on Whole-Area Lipid Layer Thickness Assessment

Abstract

Background/Objectives: Lipid layer thickness (LLT) is widely used to assess tear film status in dry eye disease (DED), but single-point measurements may not adequately reflect spatial lipid distribution driven by tear film dynamics. This study evaluated whether the combined assessment of inferior and superior corneal LLT provides additional clinical relevance for interpreting DED subtypes. Methods: This cross-sectional study included 614 eyes of 614 patients with DED. Inferior corneal LLT (LLTinf) was measured using a tear interferometer, and superior corneal LLT (LLTsup) was graded using an LED-based slit-lamp assessment. DED parameters, including meibomian gland expressibility (MGE), meibum quality, tear meniscus height, Schirmer I test, and fluorescein tear break-up patterns, were analyzed. Results: Low LLTinf showed worse meibomian gland function, with higher MGE scores than in the high LLTinf group (1.9 +/- 0.8 vs. 1.2 +/- 0.9, p < 0.001). Higher LLTinf was associated with lower aqueous parameters, and aqueous deficiency was observed in 57.4% of the high LLTinf group increasing to 83.0% when LLTsup was low. Combined LLTinf-LLTsup assessment improved the prediction of aqueous deficiency compared with LLTinf alone (AUC, 0.719 vs. 0.559). Improvement for moderate-to-severe MGD was smaller (AUC 0.731 vs. 0.653). Conclusions: LLT reflects not only lipid secretion, but also aqueous-driven distribution. The combined assessment of LLTinf and LLTsup may improve the interpretation of LLT findings and provide additional insight into tear film dynamics in DED. However, its predictive performance remains moderate, suggesting that this approach is considered a complementary interpretive framework rather than a standalone diagnostic tool.