Alterations in Corneal Nerve Structure and Function in Prediabetes

<b>Background:</b> Although prediabetes increases the risk of developing diabetes, its role in neuropathy remains unclear. We aim to assess alterations in the corneal nerve structure and function in prediabetes and risk factors for corneal nerve loss. <b>Methods:</b> An examination of IVCM and corneal sensitivity was conducted on a cohort of 75 participants, comprising 23 controls, 32 prediabetes, and 20 Type 2 diabetes. Semiautomatic analysis was employed to quantify the corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), and dendritic cell (DC) density. <b>Results:</b> CNFL and CNFD were lower in prediabetes and Type 2 diabetes than in the controls, and they were associated with DC density. CNFL and CNFD were lower in Type 2 diabetes than in prediabetes. DC density was higher in prediabetes and Type 2 diabetes than in controls. However, there were no differences in corneal sensitivity between controls and prediabetes. Multivariable regression analysis demonstrated an association between reduced CNFL and age, BMI, fasting plasma glucose (FPG), and uric acid (UA) levels in prediabetes. In Type 2 diabetes, age, HbA1c, blood urea nitrogen (BUN), creatinine (Cr), and triglyceride levels exhibited associations with reduced CNFL. <b>Conclusions:</b> Corneal nerve damage was detected in prediabetes using IVCM. The patients with prediabetes showed signs of nerve structure damage, and the corneal nerve structure damage occurred before the nerve function changes. Immune cells also participate in the occurrence and development of DCN and are related to the corneal neuropathy. Understanding the corneal nerve fiber condition through IVCM may prove crucial in monitoring prediabetic neuropathy.