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M. L. McDermott, L. Villanueva, R. Schiffman, D. A. Hollander; Comparing Corneal Epithelial Wound-Healing Effects of Ketorolac Ophthalmic Solutions in a Porcine-Derived Corneal Organ Culture Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):375.
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Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with delays in corneal wound healing. Corneal epithelial toxicity has been attributed to both the active agents and preservatives. Recently, a preservative-free formulation of ketorolac 0.45% (AcuvailTM) was introduced that also contains carboxymethylcellulose (CMC). This study was designed to evaluate the corneal wound-healing effects of commercial formulations of nepafenac 0.1% (Nevanac®, 0.005% BAK), bromfenac 0.09% (Xibrom®, 0.005% BAK), and ketorolac 0.45% in an ex vivo porcine model.
A 5 mm central epithelial lesion was made in isolated porcine corneas (n = 3-5 per group). After 24 hours, corneas were incubated with 50 µL of Minimum Essential Medium (MEM), 1% Triton X-100 detergent (TX100), or study medication for 10min. After rinsing, corneas were incubated in MEM for an additional 24 hrs. The remaining wound area was stained with Richardson’s staining solution, photographed, and quantified in pixels using Adobe Photoshop.
Corneas exposed to MEM and TX100 had a wound area of 565 ± 1263 and 59,509 ± 4850 pixels, respectively. Corneas exposed to ketorolac 0.45%, nepafenac 0.1%, and bromfenac 0.09%, respectively, had remaining wound areas of 323 ± 229, 47,323 ± 13,736 and 29,094 ± 14,295 pixels. The mean remaining wound area was significantly reduced in corneas exposed to ketorolac 0.45% compared to bromfenac (P <.01), nepafenac (P <.001) and TX100 (P <.001). The remaining wound area with bromfenac was significantly less than that of nepafenac and TX100 (P <.01). No statistical difference between nepafenac and TX100 was detected.
The removal of BAK and the addition of CMC in the ketorolac 0.45% formulation lead to more rapid corneal epithelial healing in this ex vivo model than bromfenac or nepafenac. Differences in wound healing between bromfenac and nepafenac suggest that the active ingredient or other components in the formulation, in addition to the preservative, may play a role in epithelial wound healing delays.
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