Purpose:To evaluate the ocular surface characteristics and corneal microstructure in patients with newly diagnosed Graves disease (GD) with no evidence of active thyroid eye disease (TED).Methods:Eighty eyes of 40 patients with newly diagnosed GD and 40 age-matched control subjects were recruited in this cross-sectional study. All participants underwent ocular surface tests in the order of tear break-up time (BUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire. Basal epithelial cell, keratocyte, and endothelial cell densities and subbasal nerves were evaluated using in vivo confocal microscopy (IVCM). Independent sample t test, (2) test, and Mann-Whitney U test were used for statistical analysis.Results:Patients with GD had higher OSDI (5.9 6.6 vs. 1.7 +/- 2.4, respectively, P 0.001) and LG staining scores (0.5 +/- 0.6 vs. 0.2 +/- 0.4, respectively, P = 0.003), and lower BUT scores (7.3 +/- 2.5 vs. 9.9 +/- 1.7, respectively, P < 0.001) compared with those of control subjects. Patients with GD had lower mean basal epithelial cell density (3928 +/- 657 cells/mm(2) vs. 4771 +/- 622 cells/mm(2), respectively) and total subbasal nerve density (958 +/- 394 cells/mm(2) vs. 1416 +/- 744 cells/mm(2), respectively) and higher subbasal nerve tortuosity (2.7 +/- 0.8 vs. 1.6 +/- 0.6, respectively) compared with those of control subjects (P < 0.001). There was a statistically significant negative correlation between the duration of symptoms of hyperthyroidism and BUT (rho = -0.273, P = 0.014) and a positive correlation between LG staining scores (rho = 0.329, P = 0.003). A significant reduction in BUT (rho = -0.238, P = 0.003) and epithelial cell density (rho = -0.174, P = 0.029) and an increase in OSDI scores (rho = 0.328, P = 0.003) were found with increasing exophthalmometry measurements.Conclusions:Ocular surface alterations begin early in the course of Graves disease before the onset of overt TED.