Advances in imaging of subbasal corneal nerves with micro–optical coherence tomography

Purpose: To investigate the most peripheral corneal nerve plexus using high-resolution micro–optical coherence tomography (μOCT) imaging and to assess μOCT’s clinical potential as a screening tool for corneal and systemic diseases. Methods: An experimental high-resolution (1.5 × 1.5 × 1μm)μOCTsetupwasapplied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in μOCT were compared to β3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ. Results: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm² . The repeatability of nerve density quantification of the μOCT scans as approximately 88% in multiple image recordings of the same cornea. Conclusions: Compared to the current gold standard of FCM, μOCT’s larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with μOCT’s feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy). Translational Relevance: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.