Risk Factors Associated With Corneal Nerve Alteration in Type 1 Diabetes in the Absence of Neuropathy: A Longitudinal In Vivo Corneal Confocal Microscopy Study

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The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over 4 years using in vivo corneal confocal microscopy in participants with type 1 diabetes and to identify significant risk factors associated with these alterations.


A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning in vivo corneal confocal microscopy, ocular screening, and health and metabolic assessment at baseline, and the examinations continued for 4 subsequent annual visits. At each annual visit, 8 central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density, corneal nerve branch density and corneal nerve fiber length. Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters.


A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure, or body mass index. However, corneal nerve fiber density was negatively associated with glycated hemoglobin (β = −0.76, P < 0.01) and age (β = −0.13, P < 0.01) and positively related to high-density lipids (β = 2.01, P = 0.03). Higher glycated hemoglobin (β = −1.58, P = 0.04) and age (β = −0.23, P < 0.01) also negatively impacted corneal nerve branch density. Corneal nerve fiber length was only affected by higher age (β = −0.06, P < 0.01).


Glycemic control, high-density lipid, and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage and the capability of in vivo corneal confocal microscopy for monitoring subclinical alterations in the corneal SNP in diabetes.

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