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Documentation Of Improved Ocular Surface Health After Corneal Neurotisation And Reinnervation Using Magnetoencephalography And Histology
Joseph Catapano, MD, Simon SM Fung, MD, William Halliday, MD, Cecilia Jobst, MSc, Douglas Cheyne, PhD, Emily S. Ho, B.Sc., OT Reg. (Ont.), M.Ed., Ronald M. Zuker, MD, Asim Ali, MD, Gregory H. Borschel, MD.
University of Toronto, Toronto, ON, Canada.

PURPOSE: Corneal sensation is a component of reflexes that protect the eye from injury and corneal nerves contain neuromediators that are necessary for corneal epithelial maintenance and healing. Patients with absent corneal innervation develop neurotrophic keratopathy, which is characterized by persistent corneal ulcerations, scarring and vision loss. Corneal neurotisation improves corneal sensation, but it remains unknown whether neurotisation improves ocular surface health. Other than functional sensory data, there remains a paucity of evidence documenting corneal reinnervation after neurotisation. Here we describe our experience with corneal neurotisation, including data documenting ocular surface health, magnetoencephalography and histology of corneal explants after corneal transplantation.
METHODS:Fifteen patients receiving corneal neurotisation were followed prospectively, documenting corneal sensation, ocular surface health, and visual acuity. Corneal sensation was determined using Cochet-Bonnet esthesiometry and visual acuity assessed using best spectacle corrected visual acuity (BSCVA). Magnetoencephalography (MEG) recordings were conducted in an adult patient prior to corneal neurotisation and 8 months afterward. Tactile stimuli were applied to the left and right forehead using an inflating plastic membrane tapped to the skin surface (approx. 200 stimuli at 0.8 pulses/second). The left and right corneas were also stimulated using air-puffs adjusted to the patient’s blink reflex threshold (0.6 pulses/second for 6 minutes). Source localization was carried out on the stimulus-locked averaged evoked responses (1 to 30 Hz) at 50 millisecond latency using an event-related beam-forming algorithm and superimposed on the patient’s structural (T1) MRI. Histological and immunohistochemical analysis was performed on corneal specimens from three patients undergoing corneal transplantation after neurotisation. Nerves were identified with neurofilament antibody clone 2F11 (Dako, Canada) using the DAKO Omnis platform. Neurotised corneas were compared to corneal samples obtained from six normal controls. In one patient, additional comparison was made to corneal tissue explanted from a corneal transplant prior to neurotisation.
RESULTS: Median central corneal sensation improved from 0 mm pre-operatively (range, 0 to 10) to 60 mm (range, 0 to 60) post-operatively (p < .001). After neurotisation, patients experienced fewer episodes of persistent epithelial defects and there was no further vision loss in any patient undergoing corneal neurotisation with a median follow-up of 16.4 months (range, 1.5 - 43 months). Corneal transplantation to correct pre-existing corneal scarring was uncomplicated in three patients at a median of 30 months (range, 24 - 33), with improvement in visual acuity six months post-operatively. Histological examination of explanted corneal tissue confirmed the presence of neurofilament+ axon profiles in the cornea after neurotisation. Analysis of MEG data identified a clear absence of evoked response in the anaesthetic (right) cornea prior to neurotisation. Following neurotisation, an evoked response was detected in same (right) cornea, which was localized to the ipsilateral motor cortex, suggesting that the origin of the (right) corneal sensation after neurotisation was derived from the contralateral (left) forehead.
CONCLUSION: Corneal neurotisation reinnervates the cornea using axons from the contralateral face, resulting in improved ocular surface health in addition to sensation. Corneal neurotisation permits successful corneal transplantation, giving visually impaired patients a new opportunity to regain their sight.


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