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

Abstract

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. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) 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 h of presentation with a TIA or AIS. 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). Patients with TIA and AIS 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.…”

Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis

“…Increased permeability of the BBB can be attributed to MMP related proteolytic degradation of the basal lamina and TJs [83] . MMP-9 is activated in hypoxic conditions [84] , found to be elevated in VCD [85] and stroke patients [86] as well as associated with cognitive decline and worsening neurological outcomes. Though elevated blood MMP-2 levels have also been reported in VCD subjects with multiple infarcts and stroke [87] , results for MMP-3 levels in cerebrovascular disorders were conflicting (Supplementary Table S5).…”

Spinal muscular atrophy: are small sensory fibres involved?

“…Corneal nerve loss occurs in patients with mild cognitive impairment and dementia, is related to cognitive dysfunction and functional independence and predicts conversion to dementia in subjects with mild cognitive impairment [5]. Corneal nerve loss also occurs in patients with transient ischaemic attack and stroke and is associated with cardiovascular risk factors and pial collateral status [6]. Similar to diabetic neuropathy, CCM has shown superior diagnostic performance for diagnosing multiple sclerosis, Parkinson's disease and dementia compared to gold standard testing.…”