Ocular surface changes and blink abnormalities are well-established in Parkinson's disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson's disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson's disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson's disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson's disease, ten were male and the mean age was 65.5 +/- 8.6 years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson's disease (7.56 +/- 2.4 mm/mm(2)) compared with controls (15.91 +/- 2.6 mm/mm(2)) (p < 0.0001). Corneal sensitivity did not differ significantly between the patients with Parkinson's disease (0.79 +/- 1.2 mBAR) and the control group (0.26 +/- 0.35 mBAR), p = 0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R-2 = 0.66, p = 0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinson's disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinson's disease, previously thought to be a central nervous system disorder. (C) 2017 Elsevier Ltd. All rights reserved.