Spontaneous chronic corneal epithelial defects (SCCED) in dogs: Clinical features, innervation, and effect of topical SP, with or without IGF-1

PURPOSE. To delineate the clinical features and alterations in innervation and substance P (SP) content in spontaneous chronic corneal epithelial defe cts (SCCED) in dogs and to conduct a preliminary investigation evaluating t he efficacy of topical SP, with or without insulin-like growth factor (IGF) -1, in the treatment of this disorder. METHODS. Complete ophthalmic examinations, including Cochet-Bonnet aesthesi ometry, were performed in 45 canine patients that had spontaneous corneal e pithelial defects of at least 3 weeks' duration and with no identifiable ca use. Eighteen patients had superficial keratectomies performed, and the cor neal nerves were labeled immunohistochemically with antibodies against prot ein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and ty rosine hydroxylase (TH). Relative fiber densities were assessed qualitative ly and quantitatively. Corneal epithelial cell and tear SP contents were de termined in affected and normal dogs by an enzyme immunoassay. A preliminar y open-label treatment trial of topical SP, with and without IGF-1, was con ducted in 21 dogs. RESULTS. The duration of the erosion before admittance into the study was a mean of 9.22 weeks (range, 3-52). The average patient was middle aged (mea n, 9.25 1.85 years [SD]); no sex predisposition of the disease was identifi ed. Boxers, golden retrievers, and keeshonds were overrepresented when comp ared with the normal hospital population. Corneal sensation was normal. Mar ked alterations in corneal innervation were identified in affected dogs wit h abnormal increased SP and calcitonin gene-related peptide (CGRP)-immunore active nerve plexuses identified surrounding the periphery of the epithelia l defect. The SP content of epithelial cells surrounding the defect increas ed, whereas the tear SP content remained unchanged. Of the canine patients treated with SP, with or without IGF-1, 70% to 75% had complete healing of the defect. CONCLUSIONS. This, idiopathic spontaneous corneal disease in dogs, shares c linical features with chronic epithelial defects in humans. The presence of marked alterations in peptidergic innervation and positive response to top ical therapy with SP suggest that SP plays a critical role in corneal wound -healing processes.