Corneal Neurotization Improves Ocular Surface Health And Prevents Corneal Scarring In A Rat Model Of Neurotrophic Keratopathy
Joseph Catapano, MD, PhD, Kira Antonyshyn, BSc, Gregory H. Borschel, MD.
University of Toronto, Toronto, ON, Canada.
PURPOSE: Neurotrophic keratopathy (NK) is a degenerative corneal disease that develops in patients with absent corneal sensation and innervation. In the absence of innervation, the corneal epithelium is susceptible to breakdown resulting in persistent corneal ulcerations, scarring and progressive vision loss. In severe cases, patients develop corneal perforation and blindness. Standard ophthalmic therapy fails to address the underlying loss of nerve-derived trophic support, and thus many patients continue to develop vision loss despite optimal ophthalmic management. Clinical studies have suggested that reinnervation of the cornea with corneal neurotization improves corneal sensation, ocular surface health and maintains vision in patients with NK. While promising, clinical studies are limited by the rarity and heterogeneity of NK and the inability to harvest tissue. The purpose of this study was to use a novel rat model of NK and corneal neurotization to determine whether corneal reinnervation prevents breakdown of the corneal epithelium and decreases corneal scarring. METHODS: Using a novel rat model of NK, the corneal innervation of the left cornea was ablated in ten rats; five were randomized to receive treatment with corneal neurotization after ablation. Tarsorrhaphy of the left cornea was performed in all rats to protect the corneal surface. Four weeks after ablation, the tarsorrhaphy was removed. Each rat was assessed daily with standardized photographs under normal light and with a Wood's lamp/fluorescein staining to assess corneal scarring and epithelial breakdown respectively. Area of corneal ulceration was analyzed as a percentage of the entire cornea. Data was analyzed using a Fisher's exact test or Student's t test where appropriate.
RESULTS: Seven days after removal of the tarsorrhaphy and exposure of the left cornea, a significantly larger percentage of the corneal surface in rats without corneal neurotization treatment was ulcerated in comparison to rats with corneal neurotization (30.1 % ± 12.7 vs. 0.0 % ± 0.0, p < 0.001). All rats without corneal neurotization treatment developed progressive corneal epithelial breakdown, while only one rat with corneal neurotization developed a corneal ulceration that healed within one week (p = 0.047). Eighty percent of rats without corneal neurotization developed a corneal perforation after tarsorrhaphy removal, in comparison to no rats with corneal neurotization (p = 0.008). Corneal neurotization treatment also significantly decreased corneal scarring. Figure 1 contains representative images demonstrating significant corneal scarring, perforation (A) and ulceration (B) in a rat without corneal neurotization seven days after tarsorrhaphy removal and improved ocular surface health in a rat treated with corneal neurotization (C/D).
CONCLUSION: Corneal neurotization decreases breakdown of the corneal epithelium in rats with NK and prevents perforation and scarring. This data demonstrates that axons reinnervating the cornea improve corneal epithelial maintenance and repair, although further research using this model is required to investigate the underlying mechanism. These findings support clinical studies showing that corneal neurotization improves ocular surface health and preserves vision in patients with NK.
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