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Background To develop and validate a deep learning-based approach to the fully-automated analysis of macaque corneal sub-basal nerves using in vivo confocal microscopy (IVCM). Methods IVCM was used to collect 108 images from 35 macaques. 58 of the images from 22 macaques were used to evaluate different deep convolutional neural network (CNN) architectures for the automatic analysis of sub-basal nerves relative to manual tracings. The remaining images were used to independently assess correlations and inter-observer performance relative to three readers. Results Correlation scores using the coefficient of determination between readers and the best CNN averaged 0.80. For inter-observer comparison, inter-correlation coefficients (ICCs) between the three expert readers and the automated approach were 0.75, 0.85 and 0.92. The ICC between all four observers was 0.84, the same as the average between the CNN and individual readers. Conclusions Deep learning-based segmentation of sub-basal nerves in IVCM images shows high to very high correlation to manual segmentations in macaque data and is indistinguishable across readers. As quantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management, the reported work offers utility to a variety of research and clinical studies using IVCM.

PURPOSE. The subbasal nerve plexus (SNP) is the densest and most recognizable component of the mammalian corneal innervation; however, the anatomical configuration of the SNP in most animal models remains incompletely described. The purpose of the current study is to describe in detail the SNP architecture in eight different mammals, including several popular animal models used in cornea research. METHODS.Corneal nerves in mouse, rat, guinea pig, rabbit, dog, macaque, domestic pig, and cow eyes were stained immunohistochemically with antiserum directed against neurotubulin. SNP architecture was documented by digital photomicrography and large-scale reconstructions, that is, corneal nerve maps, using a drawing tube attached to a light microscope. RESULTS.Subbasal nerve fibers (SNFs) in mice, rats, guinea pigs, dogs, and macaques radiated centrally from the corneoscleral limbus toward the corneal apex in a whorl-like or spiraling pattern. SNFs in rabbit and bovine corneas swept horizontally across the ocular surface in a temporal-to-nasal direction and converged on the inferonasal limbus without forming a spiral. SNFs in the pig cornea radiated centrifugally in all directions, like a starburst, from a focal point located equidistant between the corneal apex and the superior pole. CONCLUSIONS.The results of the present study have demonstrated for the first time substantial interspecies differences in the architectural organization of the mammalian SNP. The physiological significance of these different patterns and the mechanisms that regulate SNP pattern formation in the mammalian cornea remain incompletely understood and warrant additional investigation.