Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity

Abstract

Background Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Methods Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) in 105 patients with TIA or AIS and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 hours of presentation with a TIA or AIS. Results CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Conclusions Patients with TIA and stroke have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

“…Tear IL-6 level was shown to be inversely correlated with corneal nerve density in patients with bacterial keratitis [50]. The circulating level of IL-6 was significantly associated with corneal nerve fiber loss in patients with transient ischemic attack and acute ischemic stroke [51]. Moreover, an elegant study by Chucair-Elliott et al [52] reported that IL-6 was increased in the murine cornea after herpes simplex virus (HSV) infection, and that IL-6 suppression by either neutralizing Ab or dexamethasone reduced corneal nerve regression, thereby preserving sensation in HSV keratitis.…”

Myeloid cells protect corneal nerves against sterile injury through negative- feedback regulation of TLR2-IL-6 axis

“…49 The circulating level of IL-6 was signi cantly associated with corneal nerve ber loss in patients with transient ischemic attack and acute ischemic stroke. 50 Moreover, an elegant study by Chucair-Elliott et al 51 reported that IL-6 was increased in the murine cornea after herpes simplex virus (HSV) infection, and that IL-6 suppression by either neutralizing Ab or dexamethasone reduced corneal nerve regression, thereby preserving sensation in HSV keratitis. This notion that IL-6 contributes to corneal nerve degeneration is consistent with our ndings.…”