Deep Learning-Based Analysis of Macaque Corneal Sub-Basal Nerve Fibers in Confocal Microscopy Images

Abstract

PurposeTo describe and assess different deep learning-based methods for automated measurement of macaque corneal sub-basal nerves using in vivo confocal microscopy (IVCM).\n\nMethodsThe automated assessment of corneal nerve fiber length (CNFL) in IVCM images is of increasing clinical interest. These measurements are important biomarkers in a number of diseases including diabetes mellitus, human immunodeficiency virus, Parkinsons disease and multiple sclerosis. Animal models of these and other diseases play an important role in understanding the disease processes as efforts toward developing new and effective therapeutics are made. And while automated methods exist for nerve fiber analysis in clinical data, differences in anatomy and image quality make the macaque data more challenging and has motivated the work reported here.\n\nToward this goal, nerves in macaque corneal IVCM images were manually labelled using an ImageJ plugin (NeuronJ). Different deep convolutional neural network (CNN) architectures were evaluated for accuracy relative to the ground truth manual tracings. The best performing model was used on separately acquired macaque ICVM images to additionally compare inter-reader variability.\n\nConclusionsDeep learning-based segmentation of sub-basal nerves in IVCM images shows excellent correlation to manual segmentations in macaque data. The technique is indistinguishable across readers and paves the way for more widespread adoption of objective automated analysis of sub-basal nerves in IVCM.\n\nTranslational RelevanceQuantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management. This work reports on different approaches that, in using deep learning-based techniques, leverage state of the art analysis methods to demonstrate performance akin to human graders. In application, the approach is robust, rapid and objective, offering utility to a variety of clinical studies using IVCM.