To compare the corneal microstructure in patients with manifest keratoconus (KCN), subclinical KCN, and topographically normal relatives of patients with KCN and in healthy controls.

Prospective and cross-sectional study.

We enrolled 145 subjects in the study. The participants were divided into 4 groups, based on clinical and topographical evaluation: the manifest KCN group (n = 30), the subclinical KCN group (n = 32), the KCN relatives group (n = 53), and the control group (n = 30). Corneal microstructure was assessed by corneal in vivo confocal microscopy in all of the individuals. Mean outcome measures were basal epithelial cell density, endothelial cell density, anterior keratocyte density, posterior keratocyte density, sub-basal nerve density, sub-basal nerve diameter, and stromal nerve diameter.

The mean basal epithelial cell density, endothelial cell density, and sub-basal nerve diameter were not significantly different among the 4 groups (P = 0.057, P = 0.592, and P = 0.393, respectively). The mean anterior and posterior stromal keratocyte densities were significantly lower in the manifest group, in the subclinical group, and in the relatives group when compared with the control group (for both parameters; P < 0.001, P < 0.001, and P< 0.001, respectively). The mean stromal nerve diameter in the manifest group, subclinical group, and relatives group was significantly higher than in the control group (P = 0.001, P = 0.049, and P = 0.004, respectively).

The anterior and posterior stromal keratocyte densities were statistically lower and stromal nerve diameter was statistically higher in patients with manifest KCN, subclinical KCN, and topographically normal KCN relatives compared with controls. Confocal microscopy may be useful for the determination of early corneal microstructural changes before manifestation of typical or subtle topographic signs.