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The multipurpose NSAID: A cataract surgeon's best friend

ByEric D. Donnenfeld, MD

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As the number of available nonsteroidal anti-inflammatory drugs continues to grow, research on emerging NSAIDs continues to bring forth more information. It is important for an ophthalmologist to remember that new is not always better, as well as to remember the complications of the past. Agents such as Xibrom (bromfenac 0.9%, Ista Pharmaceuticals) and Nevanac (nepafenac 0.1%, Alcon Laboratories, Inc.) may be new to the U.S. market, but, until long-term data exist, an ophthalmologist must remain aware that safety can be an issue.

Due to its long history as a safe and efficacious NSAID, Acular (ketorolac 0.5%, Allergan, Inc.) and its newer formulation, Acular LS (ketorolac 0.4%, Allergan, Inc.), has become the gold standard for NSAIDs. Mentioned in more than 1,500 peer-reviewed publications, ketorolac has data that show its safety and efficacy. ¹ Voltaren (diclofenac, Novartis) also has been researched widely in systemic and ophthalmic use, although generic diclofenac is no longer marketed due to its association with corneal melting.^1,2 Studies of nepafenac are ongoing; the study presented for Food and Drug Administration approval provides the most information.^3-6 Oral amfenac, the active agent in nepafenac, is not commercially available, so research on its systemic use is ongoing. Bromfenac was discontinued orally because of its association with liver toxicity.⁷ It has been available in Japan and, when administered topically, appears to have a good safety profile,⁸ but further research is being conducted on its safety and efficacy.

NSAIDs and cataract surgery

NSAIDs have a number of indications in cataract surgery. Studies have been conducted to determine the perioperative benefits of NSAIDs, evaluating parameters such as pupil size, pain and anterior segment inflammation, but no study has examined the overall importance of NSAIDs in the perioperative cataract surgery arena. NSAIDs inhibit prostaglandin synthesis, subsequently inhibiting intraoperative miosis,^9-12 which complicates cataract surgery and increases the risk of capsule rupture.¹³ In a study conducted by Robert B. Snyder, MD, and colleagues, pupil size was better maintained in patients treated with ketorolac four times daily, beginning 3 days preoperatively, than in those treated with Ocufen (flurbiprofen sodium, Allergan, Inc.). ¹⁴

NSAIDs have also been proven to reduce pain during and after cataract surgery when administered preoperatively,¹⁵ and ketorolac, diclofenac, nepafenac and bromfenac have been shown to reduce anterior chamber cell and flare following cataract surgery.^5,8,16,17

NSAIDs have been proven to be effective in reducing cystoid macular edema following cataract surgery ^18-20 and in improving contrast sensitivity and quality of vision following multifocal IOL implantation. ²⁰

When should NSAID treatment be initiated?

If the objectives of NSAID prophylaxis are to reduce pain and discomfort following trauma, to treat CME following cataract surgery, to manage postoperative inflammation and to prevent intraoperative complication during cataract surgery, then when is the ideal time to start treating a patient with an NSAID?

In a masked study I conducted with a number of colleagues, we randomized 100 patients into four groups prior to phacoemulsification.²¹ The first treatment group received ketorolac 0.4% four times daily for 3 days preoperatively and one drop, administered every 15 minutes, three times immediately before surgery. The second group had the same dosage, but only for 1 day preoperatively; the third group received one drop every 15 minutes for 1 hour prior to surgery. The fourth treatment group received placebo.²¹

Data showed that patients receiving ketorolac 3 days preoperatively maintained pupil size better than the other treatment groups, with a mean difference of nearly 1.5 mm between eyes receiving ketorolac for 3 days and eyes receiving placebo (Figure 1). The enlarged pupil during surgery was associated with shorter mean surgery times (8.4 minutes for patients receiving placebo vs. 5.5 minutes for those receiving ketorolac for 3 days preoperatively) and shorter ultrasound time (2 minutes for patients receiving placebo vs. 1 minute for patients receiving ketorolac for 3 days preoperatively). Patients receiving ketorolac also had shorter phacoemulsification times (ultrasound time multiplied by ultrasound energy) than those receiving placebo (6.8 seconds mean effective phaco for patients receiving placebo vs. 5.8 seconds for patients receiving ketorolac for 1 hour preoperatively and 2.4 seconds for those receiving ketorolac for 1 day or 3 days). ²¹

Patients receiving preoperative ketorolac had better visual outcomes postoperatively than those receiving placebo (Figure 2), although the difference in visual acuity was not significant at 3 months postoperatively.²¹

Patients who received ketorolac 3 days preoperatively had a mean inflammation score of 1.6 postoperatively, compared to a mean inflammation score of 2.5 for patients receiving placebo. Pretreatment with ketorolac was also associated with improved corneal clarity at 1 day postoperatively (1.8 mean corneal clarity score for patients receiving placebo and ketorolac 1 hour before surgery vs. 1.5 mean corneal clarity score for patients receiving ketorolac 3 days preoperatively), possibly a result of using less energy intraoperatively and less postoperative inflammation.²¹ Preoperative dosing of ketorolac also reduces the amount of endothelial cell loss, with a mean loss of endothelial cell count at 235.4 for the control group vs. 104.4 for patients treated with ketorolac for 1 day preoperatively and 76.2 for patients treated with ketorolac for 3 days preoperatively, which could also account for better mean corneal clarity scores.²¹

Patients treated with ketorolac also experienced less intraoperative and postoperative pain (Figure 3) and did not require additional anesthesia; with 3 days of pretreatment with ketorolac, 8% of patients asked for additional IV sedation during surgery vs. 40% of patients without pretreatment. ²¹

Treatment with ketorolac for 1 or 3 days preoperatively also reduced the incidence of CME in patients, determined by a visual acuity of less than 20/25 and OCT findings of the macula edema. At 2 weeks postoperatively, no patients treated with ketorolac for 1 or 3 days preoperatively showed CME vs. 12% of the control group and 4% of the patients treated with ketorolac for 1 hour preoperatively. ²¹

Conclusion

The uses of NSAIDs in cataract surgery are various and numerous. NSAIDs have been shown to reduce intraoperative miosis, reduce intraoperative and postoperative pain and inflammation and reduce the incidence of CME following cataract surgery. Larger pupils during surgery often lead to faster surgical times, less viscoelastic use and shorter ultrasound and phaco times. Patients experienced better visual outcomes with at least 1 day of preoperative treatment with NSAIDs. As patient expectations rise, the NSAID will take on a larger role in a cataract surgeon’s armamentarium.

References

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