Purpose:This study aimed to compare the expression of vitamin D receptor (VDR) on the ocular surface of patients with dry eye disease (DED) and controls without ophthalmological pathologies.Methods:Patients with DED without previous treatment were studied and compared with healthy subjects. Ocular Surface Disease Index assessement and ocular surface cytology were performed in all patients. The immunohistochemical expression of VDR was evaluated using fully automated immunohistochemistry. The evaluation involved multiplying the percentage of nuclear-labeled cells (0-100) by their intensity (0-3), resulting in a score ranging from 0 to 300 (VDR H-score). Squamous metaplasia was morphologically evaluated using liquid-phase cytology with Papanicolaou/periodic acid-Schiff staining using Nelson's grade (scale 0-3, higher grade to higher metaplastic change).Results:Eighteen patients with DED without previous treatment and 10 healthy subjects were studied. Squamous metaplasia was observed in 74% of patients with DED, in contrast to 0% in the control group. In patients with DED, there was a lower expression of VDR than in the control group (VDR H-score: 11.2 +/- 13.9 vs. 80.9 +/- 56; P = 0.0001). Furthermore, an inverse correlation was observed between Nelson grade and VDR H-score (P = 0.0001, rs = -0.71). No correlation was observed between Ocular Surface Disease Index and VDR H-score.Conclusions:This is the first study to evaluate the VDR in patients with DED. These patients presented with a lower expression of VDR than healthy subjects. No correlation was found with more severe symptoms. Patients with DED also had a higher frequency of squamous metaplasia.