Bromfenac and ketorolac equally safe and effective for post-PRK treatment

A prospective, randomized, open-label study compared bromfenac 0.09% (Xibrom, ISTA) and ketorolac tromethamine 0.4% (Acular LS, Allergan) as part of a postoperative medication regimen in patients undergoing PRK. Control of pain, burning, photophobia, and foreign body sensations were similar in the two treatment groups. Both agents were safe as there was no difference in re-epithelialization between the two agents.

Key Points

Minneapolis, MN-Results of a randomized open-label trial comparing post-PRK treatment with bromfenac 0.09% (Xibrom, ISTA Pharmaceuticals) and ketorolac tromethamine 0.4% (Acular LS, Allergan) show that the two topical nonsteroidal anti-inflammatory drugs (NSAIDs) are similarly effective for minimizing patient discomfort and do not impede epithelial healing.

The multicenter study was performed at four investigational sites and included 212 eyes from 149 patients that were treated with bromfenac twice daily or ketorolac four times a day beginning after placement of a bandage contact lens. Patients having both eyes treated in the same session (174 eyes) received ketorolac in one eye and bromfenac in the other. The remaining eyes had unilateral PRK and were randomized to receive one of the two drugs.

Patients self-rated severity of pain, photophobia, burning, and foreign body sensation. Re-epithelialization was assessed by measuring the area of unhealed epithelium.

"The control of pain is one of the most crucial elements of postoperative care after surface ablation surgery. Topical NSAIDs are used for this purpose in addition to a variety of other techniques. However, among the commercially available NSAIDs, only ketorolac tromethamine 0.4% and diclofenac sodium 0.1% (Voltaren, Novartis) have an FDA-approved indication for use in refractive surgery," noted Dr. Sher.

"Bromfenac offers the convenience of twice daily dosing, and in our multicenter study enrolling a relatively large patient population, we found that bromfenac and ketorolac, when administered according to their recommended dosing schedules, were equally safe and effective."

Patients enrolled in the study were undergoing PRK for myopia or hyperopia using various laser platforms. Epithelial removal in all cases was performed over an 8.4-mm zone using an Amoils brush. Intraoperative use of mitomycin-C 0.02% for haze prophylaxis and postoperative treatment with cold balanced salt solution (BSS) were allowed.

Assignment to an NSAID group was randomized, but the treatment was open-label. Patients who underwent bilateral surgery used one NSAID in one eye and the alternate product in the fellow eye. The postoperative care regimen also included four times daily treatment with gatifloxacin 0.3% (Zymar, Allergan) and prednisolone acetate 1% (Pred Forte, Allergan).

Patient feedback

Patients were asked to rate each eye separately for severity of pain, burning, photophobia, and foreign body sensation four times a day, 10 minutes after instilling their medications, using a visual analog scale (0-10). The data were recorded in a diary, and mean scores were calculated for each postoperative day.

The pain scores showed patient discomfort was greatest on postop days one and two, with improvement thereafter. However, the peak mean pain score only reached a level of 2, and no significant differences were observed between the bromfenac and ketorolac eyes on any of the postoperative days.

The results were similar for the analyses of burning, although a mean burning score of about 2 persisted through day three. Mean severity scores for photophobia reached about 3 on the first three postoperative days and decreased on day four. However, there were no significant differences between the two NSAID groups on any of the postoperative days.

A similar pattern of results was seen for the foreign body sensation analyses.

Results of the epithelial healing measurements showed rapid healing regardless of the NSAID used and no significant differences between the two treatment groups in the area of remaining unhealed tissue on any postoperative day. In both groups, the mean unhealed area measured about 30 mm2 on day one, was reduced to about 10 mm2 on day two, and was <0.6 mm2 by day four.

"A graph plotting the unhealed area over time shows the curves for the two NSAIDs overlap and are typical of those expected after PRK," noted Dr. Sher.

He added that a recent study from Durrie et al. [Adv Ther 2007; 24:1278-1285] reported an apparent delay in epithelial healing after PRK in eyes treated with bromfenac compared with nepafenac and ketorolac.

"This is puzzling in the light of our data. The Durrie study had far fewer subjects, and the data showed that the bromfenac group had the highest range of healing times (double the standard deviation due to one outlier with a long healing time) while also being the group with the fewest subjects, only 12 eyes. Since the Durrie study dosed bromfenac off-label (with different concomitant medications) and removed the bandage lenses daily, it is difficult to directly compare this study with ours. Our study results and clinical experience demonstrate that bromfenac and ketorolac are safe and effective postop PRK medications," said Dr. Sher.