Association between High Tear Epidermal Growth Factor Levels and Corneal Subepithelial Fibrosis in Dry Eye Conditions

Abstract

To compare tear epidermal growth factor (EGF) concentration in dry eye (DE) conditions and determine correlations between EGF levels and severity of symptoms and ocular surface signs. In this prospective case-control study, 35 patients with DE, including subgroups with meibomian gland disease (MGD), Sjögren's syndrome (SS) aqueous tear deficiency, or neurotrophic keratopathy (NK), and 17 asymptomatic control subjects were evaluated. Symptoms, Schirmer test, fluorescein clearance test (FCT), EGF concentration, dye staining, and the presence of corneal subepithelial fibrosis and meibomian gland (MG) orifice metaplasia were recorded. Tear EGF and the severity of irritation and ocular surface signs were correlated. Tear EGF was higher in MGD than in the control (P = 0.03) and was lower in SS than in the control (P < 0.0001; MGD (P < 0.05) and NK (P < 0.01) groups. The DE subgroup with results in the FCT > 3 and Schirmer 1 >or= 8 had higher EGF levels than the group with FCT > 3 and Schirmer 1 < 8 and both groups with good tear clearance (P < 0.01). Tear EGF levels correlated inversely with conjunctival (r = -0.49, P = 0.0032) and corneal (r = -0.39, P = 0.022) dye staining and positively with MG orifice metaplasia (r = 0.36, P = 0.03) and corneal subepithelial fibrosis (r = 0.5, P = 0.0006). Tear EGF concentration was increased in eyes with MGD, corneal subepithelial fibrosis, and MG orifice metaplasia. Elevated tear EGF may promote development of corneal subepithelial fibrosis and lid margin changes.