Corneal Neurotization Decreases Corneal Epithelial Breakdown And Scarring In A Rat Model Of Neurotrophic Keratopathy
Joseph Catapano, MD1; Kira Antonyshyn, BSc1; Tessa Gordon, PhD2; Gregory H. Borschel, MD3
1University of Toronto, Toronto, ON, Canada, 2University of Alberta, Neuroscience and Mental Health Institute, Toronto, ON, Canada, 3The Hospital for Sick Children, Toronto, ON, Canada
Purpose:The corneal nerves are necessary to maintain corneal epithelial integrity and clarity. Patients with absent or impaired corneal innervation develop neurotrophic keratopathy (NK), characterized by recurrent epithelial breakdown, resulting in progressive corneal scarring and vision loss. Clinical studies have demonstrated that surgical reinnervation with corneal neurotization restores corneal sensation but it is uncertain whether donor nerves prevent epithelial breakdown. In a rat model of neurotrophic keratopathy, we investigated whether corneal neurotization decreases epithelial breakdown and prevents scarring in a rat model of NK.
Method: A validated rat model of NK and corneal neurotization was used. Briefly, the left corneal innervation is ablated with intracranial stereotactic electrocautery. Corneal neurotization is performed using nerve grafts and the contralateral infraorbital nerve as a donor. Rats were randomized to receive either no treatment or treatment with corneal neurotization (1:2 ratio). Rats were provided with a protective tarsorrhaphy after stereotactic ablation of the corneal innervation to prevent epithelial breakdown after surgery. Outcomes were assessed four weeks after stereotactic electrocautery of the corneal innervation to permit corneal reinnervation in rats treated with corneal neurotization. Four weeks after stereotactic ablation, the protective tarsorrhaphy was removed. The left cornea was assessed daily for seven days with standardized photographs under light and with a Wood's lamp/fluorescein staining to assess corneal scarring and epithelial breakdown. Data was analyzed using Fisher's exact test or Student's t-test where appropriate.
Results:Stereotactic ablation of the corneal innervation resulted in advanced NK in all rats not treated with corneal neurotization (n=5), including corneal epithelial breakdown, corneal ulceration, extensive corneal scarring and corneal perforation in 80% of rats. Treatment with corneal neurotization (n=10), decreased the incidence of epithelial breakdown (20%; p=0.007) and no rat developed a perforation (p=0.003). Treatment with corneal neurotization significantly decreased the area of corneal ulceration in comparison to rats with NK not receiving treatment (0.0 ± 0.0 vs. 30.1 % ± 12.7, p < 0.0001). Decreased epithelial breakdown decreased corneal scarring in rats with NK.
Conclusions: Corneal neurotization provides a surgical solution to reinnervate the cornea in patients with impaired corneal innervation. This study provides evidence that in addition to improving corneal sensation, sensory nerves reinnervating the cornea after corneal neurotization decrease corneal epithelial breakdown and scarring. Further research is required to determine how the cornea regulates nerve regrowth from donor sensory nerves and how donor nerves influence the corneal epithelium.
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