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Purpose To examine the safety and efficacy of topical anti-interleukin-1 (anti-IL-1) following photorefractive keratectomy (PRK) in rabbit eyes. Setting Joint Warfighter Refractive Surgery Center, Lackland Air Force Base, Texas, USA. Design Experimental study. Methods After standard PRK, 48 eyes of 24 New Zealand white rabbits were divided into 4 treatment arms and 1 control arm. Eyes in the treatment arms were randomized to receive fluorometholone 0.1% or an anti-IL-1 suspension (2.50 mg, 1.25 mg, or 0.25 mg doses) plus standard moxifloxacin, balanced salt solution (BSS), and an ocular lubricant (Systane) 4 times a day. Control eyes received only moxifloxacin, balanced salt solution, and ocular lubricant. Results No adverse events were observed with anti-IL-1. The safety of anti-IL-1 was affirmed because there was no statistically significant difference in time to epithelial closure, foam-layer histology and thickness, or final stromal thickness measurements between the anti-IL-1 and the steroid or control groups. No increase in haze was observed with anti-IL-1. There was a trend toward decreased haze with anti-IL-1 at several data points compared with the control and steroid groups. Finally, there was a trend toward less haze in all metrics at almost every timepoint for the 2.50 mg anti-IL-1 group compared with lesser concentrations. Conclusions Anti-IL-1 therapy might be a safe, effective alternative to steroids for haze prevention after PRK. Of the doses studied, 2.50 mg of anti-IL-1 4 times a day appeared to be most effective. Further studies in human eyes are needed. Financial Disclosure Dr. Reilly has been a consultant to Alcon Laboratories, Inc., and Abbott Medical Optics, Inc. None of the authors has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]