Corneal Stromal Microdots in Dry Eye Disease: Clinical Characterization and Associations With Corneal Nerve Parameters

Purpose: To examine whether corneal microdot accumulation is associated with dry eye disease (DED) in individuals, to demonstrate the possibility of microdots serving as a novel quantitative means to identify DED, and to analyze the correlation between microdots and in vivo confocal microscopy (IVCM) parameters. Methods: In this prospective cross-sectional study, IVCM findings were evaluated in 76 eyes of 38 DED patients and 24 eyes of 12 age-matched controls. Diagnosis of DED was based on the Dry Eye Workshop II (DEWS II) classification. IVCM images of the cornea were analyzed for microdots, corneal nerve, and epithelial immune cells (EICs). Results: Microdot deposition was significantly increased in DED patients compared with controls (P < 0.001), especially in the subepithelial stromal layer. Significantly higher numbers of subepithelial microdots were observed in severe DED compared to mild to moderate DED (P < 0.001). Multivariate generalized estimating equation (GEE) analysis revealed that microdot deposition was negatively correlated with corneal nerve fiber length (CNFL) and inferior whorl length (IWL) (P < 0.05). In contrast, microdot grades showed positive correlations with Ocular Surface Disease Index (OSDI) scores, bulbar conjunctival hyperemia, and corneal nerve tortuosity (P < 0.05). Stromal microdot grades > 2 had a sensitivity of 85.53% and a specificity of 70.83% for the diagnosis of DED. Conclusions: Patients with DED demonstrate a significant increase of microdots which correlates with corneal nerve loss. IVCM may be a powerful tool to detect corneal stromal microdots and may complement clinical examination in DED. Translational Relevance: This study identifies corneal stromal microdots as a novel, quantifiable IVCM biomarker with direct potential for objective diagnosis and stratification of DED.