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Original Investigation | Clinical Sciences

Reduction of Vitreous Prostaglandin E2 Levels After Topical Administration of Ketorolac 0.45%

Scott D. Schoenberger, MD1; Stephen J. Kim, MD1; Jinsong Sheng, MD1; M. Wade Calcutt, PhD2
[+] Author Affiliations
1Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee
2Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
JAMA Ophthalmol. 2014;132(2):150-154. doi:10.1001/jamaophthalmol.2013.5692.
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Importance  Inhibition of proinflammatory prostaglandins in the retina may have therapeutic effects for retinal disease.

Objective  To determine vitreous levels of ketorolac and prostaglandin E2 (PGE2) in eyes treated with topical ketorolac tromethamine 0.45% (Acuvail).

Design, Setting, and Participants  A 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 PGE2 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) PGE2 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 PGE2 levels. When only pseudophakic eyes were analyzed, mean (SD) PGE2 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 PGE2 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

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Figure.
Vitreous Prostaglandin E2 (PGE2) Levels

Prostaglandin E2 levels were significantly lower in patients after treatment with ketorolac tromethamine 0.45%. Error bars indicate 95% CIs.

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