Abstract
Purpose: :
To compare the PGE2 inhibition of three topical NSAIDs - ketorolac 0.45% (Acuvail), bromfenac 0.09% (Xibrom), and nepafenac 0.1% (Nevanac) in phaco patients at peak dosing levels.
Methods: :
A single center, double-masked study randomized 121 pts to receive one of three treatment arms. Pts were instructed to administer each NSAID on label at BID for ketorolac and bromfenac, and TID for nepafenac for 1 day preop. Each patient was instructed to instill one drop the morning of surgery. The patients received 4 additional doses 1 hour prior to phaco. After completion of the paracentesis site with a super blade, aqueous (0.15cc) was collected through the peripheral clear cornea with a 30 gauge needle attached to a TB syringe. Following collection, aqueous samples were stored at -60° C prior to analysis. The aqueous was diluted 1:10 with diluent and assays were conducted on multiple plates in duplicate with 7 standards per plate. Assay was conducted using a Parameter PGE2 Assay kit which is a 3.5 hour sequential competitive enzyme immunoassay designed to measure PGE2 in cell culture supernatans, serum, plasma, and urine. PGE2 values observed below the level of detection were assigned a value of 50pg/ml. An independent samples Student’s t test was used to test for between group differences.
Results: :
Ketorolac 0.45% produced the greatest inhibition of PGE2. The mean PGE2 values were 224.8 +/-164.87 pg/ml for ketorolac (n=42), 288.7 +/-226.05 pg/ml for bromfenac (n=41), and 320.4 +/-205.6 pg/ml for nepafenac (n=38). The difference between ketorolac and nepafenac was statistically significantly in favor of ketorolac (p=0.025). The comparison of ketorolac to bromfenac approached a trend in favor of ketorolac (p=0.14). The difference between bromfenac and nepafenac was not significantly different (p=0.516).
Conclusions: :
Ketorolac 0.45% (Acuvail) has a lower pH(6.8), higher concentration than previous ketorolac compounds, and contains carboxymethylcellulose with no preservatives. This new ketorolac compound achieved the greatest inhibition of PGE2 compared to nepafenac 0.1% and bromfenac 0.09%. Ketorolac was significantly more effective than nepafenac while bromfenac was not significantly more effective than nepafenac. These results suggest that ketorolac 0.45% may be more efficacious in controlling inflammation at the time of cataract surgery vs. nepafenac and bromfenac.
Clinical Trial: :
www.clinicaltrials.gov NCT01021761
Keywords: inflammation • aqueous • cataract