Corneal confocal microscopy: A valuable tool to assess effects of treatments on diabetic neuropathy

Investigators note that the capacity to visualize corneal nerves of the sub-basal plexus and stroma in real time and without requiring use of contrast agents allows for longitudinal studies that can track nerve density and arborization in the same subjects over time.

Corneal confocal microscopy has become a tool to identify small fiber neuropathy in peripheral neuropathies and neurodegenerative disease of the central nervous system.1

Corinne Jolivalt, PhD, and colleagues from the Department of Pathology, University California San Diego, explained that while the status of the corneal nerves are not yet recognized biomarkers that indicate the efficacy of clinical interventions against small fiber neuropathy and neurodegenerative disease, they undertook a diabetic mouse study to assess the efficacy of various agents against corneal nerve loss and peripheral neuropathy.

“Corneal confocal microscopy, originally developed for use in ophthalmology, is emerging as an important, non-invasive tool for identifying small fiber neuropathy in diverse clinical conditions,” the investigators said. “The capacity to visualize corneal nerves of the sub-basal plexus and stroma in real time and without requiring use of contrast agents allows for longitudinal studies that can track nerve density and arborization in the same subjects over time.”

The study2 was published in the Journal of Clinical Medicine.

According to investigators, they delivered topical ciliary neurotrophic factor (CNTF), glucagon-like peptide (GLP) analog exendin-4, and cyclopentolate to the eyes of the mice, and delivered glycopyrrolate and gallamine systemically to determine the effect on neuropathy in the animal model.

The investigators also reported that CNTF and GLP restored the corneal nerve density within 2 weeks, and cyclopentolate protected corneal nerve density while reversing indices of systemic peripheral neuropathy. Glycopyrrolate, but not gallamine, prevented multiple indices of systemic peripheral neuropathy and concurrently protected against corneal nerve loss.

“These data highlight the potential for use of corneal nerve quantification by confocal microscopy as a bridging assay between in vitro and whole animal assays in drug development programs for neuroprotectants and support its use as a biomarker of efficacy against peripheral neuropathy,” investigators concluded. “They also add support to the use of corneal nerve quantification, not only as a biomarker of diabetic neuropathy, but also of efficacy of therapeutic interventions.”

References

  • Dehghani C, Pritchard N, Edwards K, et al. Morphometric stability of the corneal subbasal nerve plexus in healthy individuals: A 3-year longitudinal study using corneal confocal microscopy. Invest Ophthalmol Vis Sci 2014;55:3195–9.
  • Jolivalt CG, Han MM, Nguyen A, et al. Using corneal confocal microscopy to identify therapeutic agents for diabetic neuropathy. J Clin Med 2022;11:2307; published online April 21, 2022; https://doi.org/10.3390/jcm11092307