Topical therapeutic strategies for the treatment of corneal fibrosis in veterinary species
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Purpose: To determine the safety and efficacy of a novel combination of TRAM-34 and ascorbic acid applied topically in vivo in native and alkali injured rabbit corneas. Methods: Twelve New Zealand rabbits were randomly assigned into 2 groups (6 rabbits/group). Native healthy eyes were treated OD BIDx5 days with either treatment (combination TRAM-34 25[mu]M (Tocris Biosciences, Bristol, UK) and ascorbic acid 10 percent (TVC)) or control (BSS). Rabbits underwent an axial corneal wound OS using an established model. Groups were treated OS BIDx5 days. Degree of corneal opacity, ocular health, safety, and efficacy were determined utilizing the Fantes grading scale and modified McDonald-Shadduck (mMS) scoring system. Immunohistochemical and microscopy techniques evaluated corneal fibrotic markers at study conclusion (day 28). Results: Combination therapy was well tolerated in all eyes, with no significant differences in mMS scores, IOP, or central corneal thickness (CCT) between treatment and control groups. Significant differences in mMS scores between groups were found at day 1 (p=0.0001), 2 (p=0.0001), 3 (p=0.0001), 4 (p=0.0285), 14 (p=0.0041) and 28 (p=0.0002). Significant differences in Fantes scores were detected between groups at day 7 (p=0.001), 14 (p=0.0027), and 28 (p=0.0001). Significant differences in CCT between groups were found at days 7 (p=0.036), 14 (p=0.0495), and 28 (p=0.0487). Laboratory testing of corneal tissues demonstrated decreased fibrosis in treatment versus control groups at day 28. Conclusions: Novel bi-modal TVC topical therapy was well tolerated and demonstrated improved corneal wound healing and reduction in fibrotic changes in TVC treated rabbits compared to controls.
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M.S.