Purpose: Nerve growth factor (NGF) has been shown to be upregulated in conditions, which damage corneal nerves and to relieve dry eye. How NGF changes in nerve injury induced by established contact lens wear is not clear. The purpose of this study was to measure the subepithelial nerve plexus and tear NGF and transforming growth factor (TGF)-β1 levels in patients with established contact lens associated with dry eye. Methods: Non-contact lens wearers and subjects who had worn soft contact lenses for more than 1 year were recruited and were divided into three groups: (1) normal controls; (2) contact lens wearers without dry eye; (3) contact lens wearers with dry eye. Corneal sensitivity was measured with a Cochet-Bonnet aesthesiometer. Nerve density and branching in the subepithelial plexus were measured using in vivo confocal microscopy. Tear NGF and TGF-β1 levels were measured with an enzyme immuno assay. Results: There was a statistically significant decrease of corneal sensitivity in contact lens wearers compared with normal controls. The nerve density in the subepithelial plexus of contact lens wearers with dry eye was 538.8 ± 39.3 μm/image (3.959 ± 0.28 pm/μm2) and 537.1 ± 30.9 μm/image (3.947 ± 0.27 pm/μm2) in those without dry eye. Both of these values were significantly (P=0.032) lower than in the normal controls (4.412 ± 0.21 pm/μm2). The concentration of tear NGF was increased in contact lens wearers with dry eye and was statistically significantly greater compared with contact lens wearers without dry eye. Transforming growth factor-β1 levels were found to increase one fold in contact lens associated dry eye, and were significantly correlated to NGF. Conclusions: Corneal subepithelial nerve density was decreased in long-term contact lens wear but this change was not significantly correlated with tear film NGF concentration. Tear film NGF levels were elevated in contact lens related dry eye, likely in response to anti-inflammatory factors such as TGF-β1.