Objectives Corneal confocal microscopy ( CCM ) is a noninvasive ophthalmic technique that identifies corneal nerve degeneration in a range of peripheral neuropathies and in patients with multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. We sought to determine whether there is any association of corneal nerve fiber measures with cognitive function and functional independence in patients with MCI and dementia. Methods In this study, 76 nondiabetic participants with MCI ( n = 30), dementia ( n = 26), and healthy age‐matched controls ( n = 20) underwent assessment of cognitive and physical function and CCM . Results There was a progressive reduction in corneal nerve fiber density ( CNFD ), branch density ( CNBD ), and fiber length ( CNFL ) ( P < 0.0001) in patients with MCI and dementia compared to healthy controls. Adjusted for confounders, all three corneal nerve fiber measures were significantly associated with cognitive function ( P < 0.05) and functional independence ( P < 0.01) in MCI and dementia. The area under the ROC curve to distinguish MCI with CNFD , CNBD , and CNFL was 69.1%, 73.2%, and 73.0% and for dementia it was 84.8%, 84.2%, and 86.2%, respectively. Interpretation CCM demonstrates corneal nerve fiber loss, which is associated with a decline in cognitive function and functional independence in patients with MCI and dementia.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) ( n = 68) or secondary progressive MS (SPMS) ( n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-μm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls ( n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD ( p = 0.004) and RNFL thickness ( p < 0.001) were lower, and CNBD ( p = 0.003) was higher. In patients with SPMS compared with controls, CNFD ( p < 0.001), CNFL ( p = 0.04) and RNFL thickness ( p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD ( p = 0.04), CNBD ( p = 0.001), CNFL ( p = 0.008) and RNFL ( p = 0.002) in RRMS; in CNFD ( p = 0.04) and CNBD ( p = 0.002) in SPMS; and in CNBD ( p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

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