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

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.

Herpetic Corneal Keratopathy Management Using Ipsilateral Supratrochlear Nerve Transfer for Corneal Neurotization.

BACKGROUND: Neurotrophic keratopathy (NK) is a potentially sight-threatening condition caused by impairment in the trigeminal corneal innervations with decrease or loss of corneal sensitivity. This prospective study aimed to evaluate the outcomes of surgical neurotization of the cornea using ipsilateral supratrochlear nerve transfer in patients with herpes-induced NK. METHODS: An ophthalmologist and a plastic surgeon performed an interdisciplinary corneal neurotization in 13 eyes of 13 patients after preoperative exclusion of forehead sensation impairment. A 3-cm supra-eyebrow incision allowed for microsurgical supratrochlear nerve dissection, and a subconjunctival tunneling was performed for the nerve transfer. Neurotrophic keratopathy was assessed preoperatively and every 3 months postoperatively using slit-lamp microscopy, the corneal sensitivity test, specular microscopy, and in vivo confocal microscopy. RESULTS: The surgeries had no major complications. The average disease duration from cornea denervation to surgery was 15.2 years. The mean follow-up duration was 18.5 ± 6 months. The symptoms exhibited subjectively improved visual acuity, and objectively improved visual analog scale and NK grading. The subepithelial corneal nerve plexus was found at 9 months postoperatively. The corneal thickness decreased and the corneal endothelial count increased postoperatively. CONCLUSIONS: This is the largest series of corneal neurotization using direct ipsilateral supratrochlear nerve transfer. It is a minimally invasive method to restore corneal sensitivity and treat NK successfully within 1 year without a sural nerve graft. A long-term follow-up is needed for further assessment.

Restoration of corneal sensation with regional nerve transfers and nerve grafts: a new approach to a difficult problem.

IMPORTANCE: Corneal anesthesia is recalcitrant to conventional treatment and can lead to permanent visual loss. OBJECTIVE: To assess the outcomes of a novel sensory reconstructive technique for the treatment of corneal anesthesia. DESIGN, SETTING, AND PARTICIPANTS: This prospective study evaluating a new technique was conducted at a tertiary referral center. Four eyes in 3 patients with corneal anesthesia underwent nerve transfers with nerve grafting to restore corneal sensation. Corneal sensory reconstruction was performed using a segment of the medial cutaneous branch of the sural nerve. Two patients with unilateral trigeminal nerve anesthesia-one following basal skull fracture and another following large posterior fossa tumor resection-underwent corneal sensory reconstruction using the contralateral supratrochlear nerve as the donor sensory nerve. One patient with a history of cerebellar hypoplasia and bilateral congenital corneal anesthesia underwent bilateral corneal sensory reconstruction using the respective ipsilateral supratrochlear nerves as the sensory donor nerves. Corneal anesthesia was evaluated preoperatively and postoperatively in the center of the cornea and in 4 corneal quadrants using a Cochet-Bonnet esthesiometer (Luneau). Complications of the procedure were also documented. MAIN OUTCOMES AND MEASURES: Esthesiometry scores. RESULTS: All eyes had prior complications of corneal anesthesia and had no measurable corneal sensation in the affected eye(s) preoperatively. Two patients-one with cerebellar hypoplasia and the other with posterior fossa tumor resection-had markedly improved corneal sensation 6 months postsurgery (3 eyes; mean [SD] central esthesiometry, 55 [5] mm). A third patient with a history of basal skull fracture underwent unilateral corneal neurotization and recovered 15-mm esthesiometry score centrally after 7.5 months of follow-up. None of the operated on eyes have developed corneal anesthesia-related complications since reconstruction. CONCLUSIONS AND RELEVANCE: Corneal sensory reconstruction provides corneal sensation in previously anesthetic corneas. This can be achieved with minimal morbidity using sural nerve grafts, which surgeons commonly use to reconstruct nerve gaps elsewhere. This multidisciplinary approach restores an ocular defense mechanism and may enable subsequent corneal transplant in these patients.

Influence of reduced neuron pool on the magnitude of naturally occurring motor neuron death.

The present investigation was undertaken to examine the role of peripheral competition in survival of motor neurons during development. A loss of approximately half of the trochlear motor neurons in duck and quail occurs during the course of normal embryogenesis. The number of motor neurons in the nucleus of quail prior to the onset of cell death is identical to the final number of survivors in the nucleus of duck embryos (about 1,300 neurons). In the present study competition at the peripheral target was decreased by reducing the number of trochlear motor neurons initially projecting to their target muscle. This was accomplished by substituting the midbrain of duck embryos with the same neural tissue from quail embryos. Midbrain transplantation was performed before motor axon outgrowth and normal cell death begin. The development of the motor neurons and their sole target of innervation, the superior oblique muscle, was examined by using a variety of techniques. The source of the grafted motor neurons and of a reduction in the size of the motor neuron pool was confirmed from histological sections and cell counts. The grafted motor neurons projected their axons into the appropriate peripheral target, which was determined by the use of HRP tracing technique. Counts of muscle fibers, motor endplates, and acetylcholine receptors and measurement of total muscle protein indicated that the size of the superior oblique muscle in the chimera embryos was similar to that of the normal duck but significantly larger than the muscle in quail embryos. Electrophysiological observations indicated that the grafted trochlear motor neurons made functional connections with the superior oblique muscle. Counts of the trochlear motor neurons after the period of cell death indicated an average of 1,310 neurons in the nucleus of duck, 772 in quail, and 690 in the chimera embryos. The number of motor neurons in the chimera embryos is not significantly different from that in the normal quail. In other words, in spite of reduced peripheral competition trochlear motor neuron death of normal magnitude occurred. Lack of increased cell survival in our study suggests that trochlear motor neurons do not compete for survival at the peripheral target.