Dry eye, a common ocular surface disease associated with tear film instability and corneal impairment, is frequently accompanied by ocular discomfort and pain. Recent research has shown that corneal nerve dysfunction may play a role in certain pathologies of dry eye
however, the details remain unclear. To clarify the aberration in corneal nerves underlying sensory abnormalities, in addition to corneal impairment in dry eye, we examined the morphological alterations of nerve fibers in the corneas excised from guinea pigs with dry eye, where the lacrimal glands were surgically excised. Guinea pigs with dry eye exhibited reduced tear volume, increased spontaneous blink frequency, and corneal epithelial damage. Simultaneously, the subbasal nerve plexus in the cornea visualized using an anti-tubulin βIII antibody partially outgrew and became convoluted. The morphology of peptidergic nerves containing calcitonin gene-related peptide, which may function as a polymodal nociceptor, was also altered. These results indicate that guinea pigs with excised lacrimal glands can serve as useful tools for investigating the neuronal mechanisms underlying corneal pathology in dry eyes. Additionally, chronic tear deficiency may considerably alter nerve structure, including peptidergic nerves in the cornea, accompanied by epithelial damage and increased blink frequency.