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

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 (LLT_inf) was measured using a tear interferometer, and superior corneal LLT (LLT_sup) 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 LLT_inf showed worse meibomian gland function, with higher MGE scores than in the high LLT_inf group (1.9 ± 0.8 vs. 1.2 ± 0.9, p < 0.001). Higher LLT_inf was associated with lower aqueous parameters, and aqueous deficiency was observed in 57.4% of the high LLT_inf group increasing to 83.0% when LLT_sup was low. Combined LLT_inf-LLT_sup assessment improved the prediction of aqueous deficiency compared with LLT_inf 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 LLT_inf and LLT_sup 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.