Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke

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.

Download Full-text

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

10.21203/rs.3.rs-301595/v1 ◽

2021 ◽

Author(s):

Adnan Khan ◽

Aijaz Parray ◽

Naveed Akhtar ◽

Abdelali Agouni ◽

Saadat Kamran ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebrovascular Disease ◽

Acute Ischemic Stroke ◽

Nerve Fiber ◽

Fiber Density ◽

Nerve Branch ◽

Vascular Integrity ◽

Markers Of Inflammation ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

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.

Download Full-text

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

Scientific Reports ◽

10.1038/s41598-018-30688-z ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 10

Author(s):

Gulfidan Bitirgen ◽

Kultigin Turkmen ◽

Rayaz A. Malik ◽

Ahmet Ozkagnici ◽

Nazmi Zengin

Keyword(s):

Dendritic Cells ◽

Confocal Microscopy ◽

Fabry Disease ◽

Nerve Damage ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

Download Full-text

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

10.21203/rs.3.rs-558220/v1 ◽

2021 ◽

Author(s):

Adnan Khan ◽

Ajay Menon ◽

Naveed Akhtar ◽

Saadat Kamran ◽

Ahmad Muhammad ◽

...

Keyword(s):

Ischemic Stroke ◽

Endothelial Cell ◽

Acute Ischemic Stroke ◽

Fibre Length ◽

Surrogate Marker ◽

Artery Occlusion ◽

Cell Parameters ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Branch Density

Abstract Background: In patients with ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collateral status will have greater corneal nerve and endothelial cell abnormalities.Method: 35 patients with acute ischemic stroke secondary to middle cerebral artery occlusion with poor (n=12) and moderate/good (n=23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology.Results: In patients with MCA stroke, corneal nerve fibre length (CNFL) (P=0.000), density (CNFD) (P=0.025) and branch density (CNBD) (P=0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p=0.023) and CNFL (p=0.026) and CNBD (p=0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from good pial collaterals with an AUC of 72% (95% CI: 53-92%) and 71% (95% CI: 53-90%), respectively. Conclusion: Corneal nerve loss is greater in patients with poor compared to good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.

Download Full-text

Corneal Confocal Microscopy Detects Alterations in Corneal Endothelial Cell Morphology in Patients Admitted with Acute Ischemic Stroke

10.5339/qfarc.2018.hbpp1004 ◽

2018 ◽

Author(s):

Adnan Khan

Keyword(s):

Ischemic Stroke ◽

Endothelial Cell ◽

Confocal Microscopy ◽

Acute Ischemic Stroke ◽

Cell Morphology ◽

Corneal Endothelial Cell ◽

Corneal Confocal Microscopy

Download Full-text

Corneal nerve loss as a surrogate marker for poor pial collaterals in patients with acute ischemic stroke

Scientific Reports ◽

10.1038/s41598-021-99131-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adnan Khan ◽

Ajay Menon ◽

Naveed Akhtar ◽

Saadat Kamran ◽

Ahmad Muhammad ◽

...

Keyword(s):

Ischemic Stroke ◽

Endothelial Cell ◽

Acute Ischemic Stroke ◽

Nerve Fibre ◽

Fibre Length ◽

Surrogate Marker ◽

Nerve Branch ◽

Cell Parameters ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

AbstractIn patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53–92%) and 71% (95% CI 53–90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.

Download Full-text