Corneal nerve beadings size detected by in vivo confocal microscopy in uncomplicated type 1 diabetes mellitus: a novel algorithm

Abstract

Purpose : Corneal sub basal nerve plexus (SBP) characteristics could be detected using in vivo confocal microscopy (IVCM).
These features include hyper-reflective, focal enlargement of nerve axons, named beadings, that seems to be an accumulation of mitochondria, glycogen and vesicles.
Previously in literature, corneal beadings alterations in patients with type 2 diabetes mellitus have been reported.
We study if a population of type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications presents similar beadings alterations in number and size.

Methods : We implemented a new algorithm to automatically identify and number beadings and measure their size in SBP captured using IVCM.
6 eyes of 6 patients aged >18 years with uncomplicated T1DM (without diabetic peripheral or autonomic neuropathy, diabetic retinopathy and microalbuminuria) and 11 eyes of 11 healthy controls underwent a complete ophthalmological evaluation and IVCM, performed with z-scan ring (Confoscan 4; Nidek Technologies, Padova, Italy).
The best-focused frame was chosen. We cropped 0.1 mm of corneal nerve for each SBP image.The Mann-Whitney test was used for statistical analysis.

Results : There was no differences in mean number of corneal beadings for 0.1 mm of SBP nerve between T1DM and healthy controls (T1DM=10.17± 0.65 vs controls=10.82 ±0.66 , p=0.382). Our automatic count of beadings resulted substantially in agreement with automatic count of corneal nerve fiber using CS4 Nerves Tracking software and manual revision, that was carried out by two experienced operator (D.S.L. and I.A.).
Regarding the beadings size, our automatic algorithm identified a mean area of corneal beadings in T1DM patients higher than the mean area of healthy controls. This difference was statistically significant (T1DM= 11.72 ±1.48 µm² vs controls=7.55 ±0.35 µm², p= 0.002)

Conclusions : Mitochondrial dysfunctions seems to play an important role in diabetic neuropathy onset.
We already reported that T1DM patients even in good glycemic and metabolic control showed SBP parameter alterations, but the number and density of beadings did not statistically differ compared to healthy patients.
Nevertheless, using this new algorithm, we show that beadings are enlarged in a small highly selected population of T1DM.
Identify beading expansion in corneal nerve fiber using IVCM could be an useful tool to predict peripheral neuropathy.

This is a 2020 ARVO Annual Meeting abstract.