In Vivo and Ex Vivo Comprehensive Evaluation of Corneal Reinnervation in Eyes Neurotized With Contralateral Supratrochlear and Supraorbital Nerves

Abstract

Purpose: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. Methods: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with “ACCMetrics;” neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. Results: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. Conclusions: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea

“…PED is a sight-threatening condition that can result in corneal melting, perforation and severe vision loss. Treating PED is challenging for ophthalmologists and surgical intervention, such as AMT or tarsorrhaphy, or even new techniques such as corneal neurotization are occasionally indicated to manage refractory cases that are unresponsive to medical therapy (Katzman & Jeng 2014;Giannaccare et al 2020). Recently, the use of topical insulin has reportedly yielded satisfactory results in several small case series of PED patients, posing as a possible effective alternative to autologous serum (Diaz-Valle et al 2020).…”

Topical insulin for refractory persistent corneal epithelial defects

“…11,12 Furthermore, a new surgical procedure, corneal neurotization, has been shown to improve epithelial healing, corneal sensation, and reinnervation in patients with neurotrophic PED. 13 When the epithelium loses its integrity, it heals through activation of stem cells residing in the corneoscleral junction that are stimulated by growth factors, cytokines, and extracellular matrix signals. 14 Myofibroblasts develop within the surface of PEDs and if the condition persists, a more disordered extracellular matrix is secreted by these cells.…”

Maternal serum eye drops to treat bilateral neurotrophic keratopathy in congenital corneal anesthesia: Case report and literature review

“…Among new surgical procedures, the recent introduction of corneal neurotization opens new perspective in the treatment of (pediatric) NK. 18 , 19 , 20 , 21 , 22 …”