CSNs play an essential role in maintaining ocular surface health and vision as a result of preserving corneal integrity and sensation.
5 Recently, IVCM has become a widely used noninvasive diagnostic tool for the clinical evaluation of the cornea, which ensures high-resolution images of corneal nerves, structures, and layers.
10 Jiang et al.
18 reported that noninvasive IVCM imaging of CSN is a practical and useful method to determine the alterations of small fiber neuropathy. Because previous studies have reported a high agreement in the evaluation of corneal nerves between IVCM and histologic examinations, IVCM has been used to evaluate qualitative and quantitative variations of the corneal nerves in many conditions, including herpes zoster ophthalmicus, corneal transplantation, laser refractive surgery (laser-assisted epithelial keratomileusis and photorefractive keratectomy), noncorneal ocular procedures (cataract surgery, laser panretinal photocoagulation, laser retinopexy, and scleral buckles), antiglaucoma medical therapy (particularly topical beta-adrenergic antagonists), aging, diabetes mellitus, and dry eye.
19–29 A significant decrease in CSN density has been shown nearly in all of these conditions. Most of the studies investigating corneal nerves in DED patients also mainly assessed the CSN density and found a decrease in the majority, whereas others found an increase or no change.
30–33 These variable results were found to be associated with differences in DED severity, corneal nerve damage severity, neural regeneration/degenerative patterns, and inflammation levels.
13 Recently, Stepp et al.
34 have demonstrated that decreased intraepithelial corneal nerves in the CD25 null Sjögren syndrome mouse model is accompanied by reduced corneal sensitivity and increased corneal epithelial cell proliferation. Furthermore, Stepp et al.
35 reported a significant decrease in axon thickness, density, and apical extension of the intraepithelial nerve terminals after 5 days of dry eye exposure in C57BL/6 mice. Additionally, a previous study done by De Paiva et al.
36 has shown acute deterioration of barrier function and increased inflammation even after 5 days of desiccating stress in mice. Similarly, we found a notable decrease in subbasal nerve density after acute environmental stress in our previous study.
13 In the current study, 28 days of dry eye stress reduced CSN density in the WT mice.