Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke

Abstract

Objectives Corneal nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater corneal nerve damage in patients with recurrent ischemic stroke. Methods Corneal confocal microscopy (CCM) was used to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and corneal nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects. Results Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA 1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA 1c , total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14).

Corneal Nerve Loss in Patients with Acute Ischemic Stroke: A Surrogate Marker for Poor Pial Collaterals

“…In this translational study, we show evidence of corneal nerve loss in patients with acute MCA stroke compared to healthy controls, which agrees with our recent studies showing corneal nerve loss in patients with TIA 23 , acute 20,22 and recurrent stroke 21 . Moreover, we show that corneal nerve loss was greater and there was good diagnostic accuracy for differentiating patients with poor compared to moderate-good pial collaterals, despite comparable blood pressure, lipids and HbA 1c .…”

“…CCM has emerged as a powerful non-invasive ophthalmic imaging endpoint to identify corneal nerve loss in patients with multiple sclerosis 38 , Parkinson's disease 39 , dementia 40 and patients with acute ischemic stroke 20 and recurrent stroke 21 . We now show that CCM identi es greater corneal nerve loss in patients with poor compared to moderate/good pial collaterals.…”

“…Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that has been used to demonstrate axonal loss in patients with impaired glucose tolerance 16 , diabetes 17,18 , and other peripheral neuropathies 19 . Recent studies have also demonstrated a signi cant reduction in corneal nerves [20][21][22] and abnormalities in endothelial cells in patients with TIA 23 and acute ischemic stroke 22 . We have also shown that corneal nerve loss is associated with age, HbA 1c , lipids and blood pressure 18 and the presence of white matter hyperintensities 24 in patients with acute ischemic stroke.…”

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

“…Moreover, we now show that the severity of corneal nerve loss is comparable between patients with TIA and major stroke. Recently, we have also shown greater corneal nerve loss in patients with recurrent stroke, despite comparable vascular risk factors [27].…”

“…Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that has identi ed corneal nerve loss in patients with diabetic neuropathy [16][17][18], other peripheral neuropathies [19], multiple sclerosis [20,21] and dementia [22]. Recently, we have shown a signi cant loss of corneal nerves in patients with TIA [23], acute ischemic stroke [24][25][26] and recurrent stroke [27] indicating that it may be a surrogate marker for the risk of stroke. Increased plasma adhesion molecules including P-selectin and ICAM-1 predict the development of diabetic neuropathy over 5 years [28] and elevated IL-6 has been associated with distal neuropathy in subjects with impaired glucose tolerance [29].…”