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David Culp, Elizabeth Schaefer, Maria-Grazia Spiga, Aliah Hackney, Nicholas Smith, Brian C Gilger; Characterization of a quantitative model of corneal inflammation, wound healing, and fibrosis in the rabbit. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1286. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To develop and characterize a sensitive and translatable model of corneal wound healing and fibrosis in the New Zealand White Rabbit.
An 8 mm central corneal defect of approximately 10-15% stromal depth was created using a corneal trephine and lamellar resection. Dexamethasone (DEX) or balanced salt saline (BSS) were administered topically 4 times a day for 28 days after keratectomy. Hackett-McDonald (HM) ocular inflammatory scores and area of fluorescein positive staining to evaluate re-epithelialization were evaluated every 12 hours for 5 days, then weekly through 28 days. Stromal fibrosis, haze, and corneal thickness were measured by SD-OCT (Envisu, Bioptigen) and histopathology at 12, 24 and 48 hours and on days 7 and 28.
Cumulative HM scores were significantly lower in eyes treated with DEX compared to BSS for the first 4 days after surgery; however, area of fluorescein retention (re-epithelialization of the wound) was higher in DEX compared to BSS-treated eyes through 7 days and time to complete re-epithelization was longer by 3 days in DEX vs BSS eyes. On SD-OCT, corneal opacity scores on day 7 were similar between DEX and BSS treated eyes, but by day 28 there was a 60% reduction in stromal fibrosis in DEX treated eyes. Histologic scores in the anterior segment and cornea were consistently lower in DEX treated eyes on both 7 and 28 days after keratectomy.
Using this corneal wound healing model, we demonstrated that topical DEX inhibited ocular inflammation, corneal fibrosis, and opacity compared to BSS. This keratectomy model allows quantitative assessment of specific anti-inflammatory and wound healing therapies, and can be used in pre-clinical development to provide effective proof of concept of novel compounds or delivery methods.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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