Potential New Modes of Treatment of Neurotrophic Keratopathy

Abstract

The cornea focuses external light onto the retina, a function for which it must be transparent and possess a smooth surface. Homeostasis of the corneal epithelium is regulated by various humoral factors present in the tear fluid and by neural factors derived from the trigeminal nerve. Neurotrophic keratopathy (NK) is characterized by corneal epithelial disorders that result from impairment of trigeminal nerve function and a consequent deficiency of neural factors. The ideal mode of treatment for this condition is the regeneration of damaged trigeminal nerve fibers, but such therapy is not currently available. In this review, we describe established and potential new treatments of NK. Our research demonstrated that a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1) has a synergistic stimulatory effect on corneal epithelial migration in vitro and on corneal wound closure in vivo. Furthermore, we identified the minimal amino acid sequences of substance P and IGF-1 required for this synergistic action based on the assumption that the clinical application of peptides corresponding to these sequences would have fewer side effects compared with the full-length molecules. Combination of the substance P-derived peptide FGLM-amide and the IGF-1-derived peptide SSSR promoted corneal epithelial wound healing in patients with NK.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01756456.

Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves

“…The experimental evidence that SP is able to promote corneal healing has prompted some small open‐label clinical studies in patients with NK, which demonstrated an efficacy of topical SP associated with IGF‐1 treatment in in promoting corneal wound healing. Subsequently, topical SP and IGF‐1 treatment were evaluated in a larger, open‐label study in 25 patients with NK, achieving a complete corneal healing in 73% of patients after 4 weeks of treatment (Brown et al, ; Chikama et al, ; Nishida et al, ; Yamada et al, ; Yanai et al, ).…”

Update on corneal neurotisation

“…Antibiotic drops are needed to prevent bacterial infections in addition to ocular surface lubrication. Options include corneal and scleral contact lenses,29 a lateral tarsorrhaphy, botulinum A toxin into the levator muscle or amniotic membrane transplantation to cover the non-healing epithelial defect 30. Treatment of stage 3 disease is directed at stopping the stromal melting to prevent perforation 31.…”

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

“…As such, current therapy is directed toward alleviating symptoms as they appear. Some commonly used treatments include artificial tears, bandage contact lenses, punctual occlusion, autologous serum tears, tarsorrhaphy, and amniotic membrane grafting (Nishida and Yanai, 2009; Yanai et al, 2015). Local administration of neural factors such as substance-P (SP), particularly in combination with insulin-derived growth factor-1 (IGF-1), has been shown to promote epithelial cell migration and closure of persistent epithelial defects in the setting of NK (Yanai et al, 2015).…”

“…Some commonly used treatments include artificial tears, bandage contact lenses, punctual occlusion, autologous serum tears, tarsorrhaphy, and amniotic membrane grafting (Nishida and Yanai, 2009; Yanai et al, 2015). Local administration of neural factors such as substance-P (SP), particularly in combination with insulin-derived growth factor-1 (IGF-1), has been shown to promote epithelial cell migration and closure of persistent epithelial defects in the setting of NK (Yanai et al, 2015). Nerve growth factor (NGF) has also been shown to promote wound healing and induce nerve regeneration in neurotrophic corneas but local adverse effects have limited its use (Nishida and Yanai, 2009).…”