Validation of the Use of Automated and Manual Quantitative Analysis of Corneal Nerve Plexus Following Refractive Surgery

Abstract

Following refractive surgery, the cornea is denervated and re-innervated, hence a reproducible tool to objectively quantify this change is warranted. This study aimed to determine the repeatability and reproducibility of corneal nerve quantification between automated (ACCMetrics) and manual software (CCMetrics) following refractive surgery. A total of 1007 in vivo confocal microscopy images from 20 post-small incision lenticule extraction (SMILE) or post-laser-assisted in situ keratomileusis (LASIK) patients were evaluated by two independent observers using CCMetrics for corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fibre length (CNFL). Intra-observer and inter-observer reproducibility and repeatability, as well as agreement and correlation between the measurements obtained by ACCMetrics and CCMetrics, were assessed. We found that CNFL demonstrated the best intra- and inter-observer agreement followed by CNFD (intra-class correlation coefficient (ICC) = 0.799 and 0.740, respectively for CNFL; 0.757 and 0.728 for CNFD). CNBD demonstrated poorest intra- and inter-observer ICC. There was an underestimation in ACCMetrics measurements compared to CCMetrics measurements, although the differences were not significant. Our data suggested that both automated and manual methods can be used as reliable tools for the evaluation of corneal nerve status following refractive surgery. However, the measurements obtained with different methods are not interchangeable.

Diabetic Corneal Neuropathy

“…Moreover, the corneal subbasal nerve plexus is the densest and most recognisable component of the corneal innervation; hence, it has been considered as an anatomical landmark to assess corneal nerve morphology. The high reproducibility of IVCM to evaluate the corneal subbasal nerve plexus quantitatively [42] makes it increasingly important for clinicians to assess corneal nerve changes objectively (Section 5.2.5).…”

Semiautomated and Automated Quantitative Analysis of Corneal Sub-Basal Nerves in Patients With DED With Ocular Pain Using IVCM

“…In our study, due to a lack of appropriate software and hardware, we relied on the widely used standard IVCM image extraction approach (29). Our study applied the well-accepted method of averaging the values of the five sites to represent the overall SNP of the eye (11). In the process of photographing and image selection, we tried to select images containing non-repeating SNP.…”

“…At the present, quantitative applications for evaluating corneal nerves range from fully manual (CCMetrics, University of Manchester, Manchester, UK) to semiautomated (NeuronJ, with ImageJ plugin, National Institutes of Health, Bethesda, MA, USA) to fully automated (ACCMetrics, University of Manchester, Manchester, UK), all of which generate varying degrees of quantitative nerve evaluation (11). Due to the laborious and time-consuming nature of applying fully automated CCMetrics software, the fully automated CCMetrics approach has been replaced with the semiautomated NeuronJ technique (12).…”

Comparing the results of manual and automated quantitative corneal neuroanalysing modules for beginners

“…Other less commonly examined morphometric parameters include beading, branching, reflectivity, and fiber diameter 16 , 17 . All these parameters have been used in past studies to evaluate corneal nerve; however, the most reliable method for quantitative neuroanalysis has not yet been concluded 18 – 21 .…”

“…Automated module software, ACCMetrics (ACCM, Automated tracing of nerve fibers, Manchester University, Manchester, UK), was later developed to perform automatic analysis of nerve parameters. Some previous studies have compared the measurements of CCM and ACCM modules, and the results were not considered interchangeble 18 , 22 . Due to the non-desirable performance of automated software, some studies recruited less experienced observers or used crowdsourcing to perform large-volume image interpretation, as formal training for neuroanalysis is time- and labor-consuming.…”