Reformulated NSAID reduces pain, inflammation after cataract surgery

Eric D. Donnenfeld

A reformulated ophthalmic NSAID effectively treated pain and inflammation and improved vision after cataract surgery, a study found.

Investigators set out to gauge the safety and efficacy of Acuvail (ketorolac tromethamine ophthalmic solution 0.45%, Allergan) administered twice daily. The reformulated agent is designed to equal the efficacy of earlier 0.5% and 0.4% formulations, with improved tolerability and less frequent dosing, the study authors said.

“Ketorolac 0.45% is the best-tolerated NSAID I have ever worked with, and this is shown in the FDA trial,” Eric D. Donnenfeld, MD, corresponding author and OSN Cornea/External Disease Board Member, said in an email interview. “Considering the drug’s effectiveness against post-cataract inflammation, ketorolac 0.45% seems to combine the efficacy of the previous ketorolac formulations with improved tolerability and a less frequent dosing regimen.”

Ketorolac 0.45% is approved by the U.S. Food and Drug Administration for control of inflammation and pain after cataract surgery. It is used off-label to improve visual acuity.

A significantly higher percentage of patients treated with reformulated ketorolac gained three or more lines of best corrected visual acuity compared with patients who underwent sham treatment, Dr. Donnenfeld and colleagues reported.

The study was published in the American Journal of Ophthalmology.

Study design and endpoints

The two prospective, randomized, double-masked phase 3 clinical trials conducted at 48 centers included 511 cataract patients randomized 2:1 to receive ketorolac or vehicle in the operated eye from 1 day before surgery to 14 days after surgery. Of 511 patients, 340 received ketorolac and 171 received the vehicle.

Patients with uncontrolled ocular disease, active eye inflammation, history of chronic or recurrent inflammatory eye disease, previous intraocular surgery aside from refractive procedures, or known contraindications to study medications were excluded.

Patients who used ophthalmic analgesics, steroids or immunosuppressants, NSAIDs or prostaglandins within 14 days before randomization, or had a history of using tamsulosin hydrochloride were also excluded.

An automated telephone voice response system was used to collect patient ratings of ocular pain. Ratings ranged from 0 (no pain) to 4 (intolerable pain). Patients called the system twice daily for 2 weeks after surgery, once in the morning and once in the evening, about 1 hour after drug instillation.

The primary efficacy endpoint was percentage of patients with a summed ocular inflammation score (SOIS) of 0 for anterior chamber cell and flare on day 14. SOIS ranged from 0 (no inflammation) to 8 (severe inflammation). The SOIS was the sum of scores for anterior chamber cells and flare in the operated eye.

The secondary endpoint was percentage of patients with no pain (grade 0) on postoperative day 1. Other endpoints included time to postoperative pain resolution, completion of the study without the use of other medications for pain or inflammation, pupil size after irrigation and aspiration, and safety. Visual acuity was evaluated ad hoc.

Investigators reported the percentage of patients who had an increase in BCVA of three or more lines.

Patients were evaluated 1, 3, 7 and 14 days after surgery.

BCVA, pain and inflammation

Study results showed that 52.5% of ketorolac patients and 26.5% of vehicle controls had an SOIS of 0 at 14 days after surgery. The difference was statistically significant (P < .001).

Significantly more patients in the ketorolac group gained three or more lines of BCVA than controls at 7 days and 14 days after surgery. At 7 days, 54.4% of patients in the ketorolac group and 39.1% of controls gained three or more lines (P = .003). At 14 days, 60.5% of ketorolac patients and 44% of vehicle patients gained three or more lines (P = .002).

“Excellent vision is the most important outcome of cataract surgery,” Dr. Donnenfeld said. “These findings suggest that perioperative use of ketorolac may help to improve the [visual acuity] of patients undergoing intraocular surgery.”

The median time to pain resolution was 1 day for the ketorolac patients and 2 days for the vehicle patients; the variance was statistically significant (P < .001).

Results also showed that 81.2% of ketorolac patients and 57.1% of vehicle controls completed the study without requiring other medications for pain or inflammation. The difference was statistically significant (P = .001).

Further study is warranted to compare perioperative use of ketorolac 0.45% with other NSAIDs, the authors said. – by Matt Hasson

Reference:

• Donnenfeld ED, Nichamin LD, Hardten DR, et al. Twice-daily, preservative-free ketorolac 0.45% for treatment of inflammation and pain after cataract surgery. Am J Ophthalmol. 2011;151(3):420-426.

• Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; email: eddoph@aol.com.
• Disclosure: Dr. Donnenfeld is a consultant to Allergan, Abbott Medical Optics and Alcon.