AUTHOR=Ponirakis Georgios , Al-Janahi Ibrahim , Elgassim Einas , Homssi Moayad , Petropoulos Ioannis N. , Gad Hoda , Khan Adnan , Zaghloul Hadeel B. , Ali Hamda , Siddique Mashhood A. , Mohamed Fatima F. S. , Ahmed Lina H. M. , Dakroury Youssra , El Shewehy Abeer M. M. , Saeid Ruba , Mahjoub Fadwa , Al-Thani Shaikha N. , Ahmed Farheen , Hussein Rawan , Mahmoud Salah , Hadid Nebras H. , Al Obaidan Aisha , Salivon Iuliia , Mahfoud Ziyad R. , Zirie Mahmoud A. , Al-Ansari Yousuf , Atkin Stephen L. , Malik Rayaz A. 

TITLE=Sustained corneal nerve loss predicts the development of diabetic neuropathy in type 2 diabetes

JOURNAL=Frontiers in Neuroscience

VOLUME=18

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1393105

DOI=10.3389/fnins.2024.1393105

ISSN=1662-453X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D).</p></sec><sec id="sec2"><title>Methods</title><p>Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4–7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, &lt;24 fibers/mm<sup>2</sup>), corneal nerve branch density (CNBD, &lt;21 branches/mm<sup>2</sup>), and corneal nerve fiber length (CNFL, &lt;16 mm/mm<sup>2</sup>) persisting for ≥50% of the study duration.</p></sec><sec id="sec3"><title>Results</title><p>A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage (<italic>p</italic> &lt; 0.0001). Sustained corneal nerve damage was associated with the development of DPN (<italic>p</italic> &lt; 0.0001), a progressive loss of vibration perception (<italic>p</italic> ≤ 0.05), an increased incidence of burning pain, numbness, or a combination of both (<italic>p</italic> = 0.01–0.001), and a borderline association with progressive sudomotor dysfunction (<italic>p</italic> = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9–86.8%, <italic>p</italic> &lt; 0.0001), while baseline and other sustained measures did not predict DPN onset.</p></sec><sec id="sec4"><title>Conclusion</title><p>Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction.</p></sec>