Reduction of Vitreous Prostaglandin E₂Levels After Topical Administration of Ketorolac 0.45%

Abstract

IMPORTANCE Inhibition of proinflammatory prostaglandins in the retina may have therapeutic effects for retinal disease. OBJECTIVE To determine vitreous levels of ketorolac and prostaglandin E 2 (PGE 2 ) in eyes treated with topical ketorolac tromethamine 0.45% (Acuvail). DESIGN, SETTING, AND PARTICIPANTSA prospective comparative interventional study, performed in a university academic hospital, included 24 eyes in 22 consecutive patients undergoing pars plana vitrectomy. INTERVENTION Application of topical ketorolac 0.45%, 4 times daily, for 3 days before pars plana vitrectomy in the first 12 consecutive eyes. The next 12 eyes were untreated and served as controls. Undiluted vitreous samples were obtained at the time of surgery and immediately frozen at −80°C. MAIN OUTCOMES AND MEASURES Vitreous ketorolac and PGE 2 levels.RESULTS Seven of the 12 eyes (58%) had ketorolac levels above the lower limit of quantitation. All 7 were in pseudophakic eyes, and 4 of the 5 below this limit were phakic (P = .01). The mean ketorolac level in the 7 eyes was 7.55 ng/mL (range, 5.0-14.9 ng/mL). The mean (SD) PGE 2 levels were 13.8 (3.8) pg/mL in control eyes and 11.7 (4.4) pg/mL in ketorolac-treated eyes (P = .04). Treatment with ketorolac resulted in a 15% reduction in PGE 2 levels. When only pseudophakic eyes were analyzed, mean (SD) PGE 2 levels were 14.1 (4.1) pg/mL in control eyes and 11.6 (4.5) pg/mL in ketorolac-treated eyes (P < .05).CONCLUSIONS AND RELEVANCE Topical ketorolac 0.45% can obtain a vitreous level that exceeds its median inhibitory concentration and can significantly decrease vitreous PGE 2 levels. Vitreous levels of ketorolac were significantly higher in pseudophakic eyes than in phakic eyes. The results of this study suggest that topically administered ketorolac 0.45% may allow meaningful inhibition of prostaglandins in the retina. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01609881 JAMA Ophthalmol. 2014;132(2):150-154.

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