Abnormal corneal nerve morphology and brain volume in patients with schizophrenia

Adnan Khan,Ahmed Elsotouhy,Ahmed Own,Reem Ghandi,Georgios Ponirakis,Anjushri Bhagat,Majid Alabdulla,Hanadi Al Hamad,Amani Ahmed,Rayaz A Malik,Mahmoud Khalil Mahmoud Alshawwaf ,James Currie,Marwan Ramadan,Mohamed Adil Shah Khoodoruth,Peter Woodruff ,Surjith Vattoth,Peter M Haddad,Hoda Gad,Ziyad Mahfoud,Ioannis N Petropoulos

doi:10.1038/s41598-022-05609-w

Abstract

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35–0.86 and P = 0.50) or cognitive function (P = 0.35–0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61–0.64) or diabetes (P = 0.057–0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.

Highlights

Corneal nerves in the sub-basal plexus are comprised of unmyelinated C-fibers that convey thermal and mechanical sensation to protect the eye from injury[13]
This study shows evidence of reduced corneal nerve fibers and cingulate gyrus volume in patients with schizophrenia
Corneal nerve fiber loss in patients with schizophrenia was not associated with diabetes or metabolic syndrome

Summary

Introduction

Corneal nerves in the sub-basal plexus are comprised of unmyelinated C-fibers that convey thermal and mechanical sensation to protect the eye from injury[13]. Corneal confocal microscopy (CCM) is a rapid noninvasive ophthalmic imaging technique that has been utilized to demonstrate corneal nerve loss in a range of peripheral neuropathies including diabetic neuropathy[14], HIV neuropathy[15], and recently long-COVID16. We and others have shown corneal nerve fiber loss in patients with d ementia[17] and multiple s clerosis[18]. It is hypothesized that patients with schizophrenia will have evidence of corneal nerve loss independent of other risk factors for neuropathy, including metabolic syndrome and diabetes. This is the first study to quantify corneal nerve pathology and regional MRI brain volumes in relation to symptom severity and cognitive function in patients with schizophrenia

Methods

Results

Conclusion