Patients undergoing cataract surgery today have high postoperative expectations. This means that we as ophthalmologists must be proactive in providing effective, comfortable, and safe pre- and postoperative care. The use of topical nonsteroidal antiinflammatory drugs (NSAIDs) assists us in this effort by reducing corneal pain, maintaining a large pupil, and controlling postoperative inflammation.

NSAIDs have become mainstream. Most ophthalmologists prescribe them to prevent the development of cystoid macular edema (CME), but our definition of CME has evolved over the last decade. We used to base our decision on whether CME was visually significant on Snellen visual acuity, and we diagnosed it with angiography. However, patients continued to complain about their quality of vision, even in the presence of angiographic CME. Clinicians considered that visually insignificant because patients still had good Snellen visual acuity. Today’s cataract surgery is completely different; it has come of age. This article discusses how NSAIDs work from a clinical perspective to provide the best quality of vision possible.

CME
Based on my experience with LASIK, I have come to understand that there are more sensitive ways to evaluate vision, which include patients’ perceptions of their vision and contrast sensitivity testing. I learned this in the refractive surgery realm and now in the cataract surgery realm. A more sensitive objective measurement of CME has developed through the advent of optical coherence tomography analysis. In a recent study, researchers found that statistically significantly less ocular thickening occurred in patients for whom an NSAID and a steroid were used.1 They also found improved contrast sensitivity testing.

OTHER USES OF NSAIDs
PRK studies have proven that patients experience a small amount of corneal pain and choroidal discomfort from clear corneal incisions and limbal relaxing incisions. NSAIDs can minimize this pain, but most cataract surgeons typically use NSAIDS during cataract surgery to treat postoperative inflammation, not corneal pain.

Additionally, NSAIDs maintain a well-dilated pupil during cataract surgery, making the procedure less complicated complicated. They improve visualization for the surgeon, which facilitates the cataract procedure, particularly the creation of the capsulorhexis and the removal of the cataract. Studies by Calvin W. Roberts, MD, and Eric D. Donnenfeld, MD, demonstrated that NSAIDs, when administered before cataract surgery, produce a larger pupil that is less likely to constrict during surgery.²

Surgeons use NSAIDs primarily to treat postoperative inflammation. Studies by Dr. Roberts, Dr. Donnenfeld, Stephen Lane, MD, others, and myself have shown that NSAIDs effectively reduce postoperative inflammation after cataract surgery.^1-3 When I began investigating this class of drugs 10 to 15 years ago, roughly two out of 10 physicians were actually using NSAIDs for routine cataract surgery. Today, most physicians use these agents. Minor inflammation follows routine cataract surgery, and more importantly, a small degree of retinal thickening occurs that can be clinically significant.^1,4

INITIATING NSAIDs
During cataract surgery, prostaglandins are released when the surgeon creates the first incision, starting a cascade of inflammation. Placing a patient on NSAIDs before surgery helps achieve maximal stabilization of the bloodaqueous barrier and prevents inflammation.

Research by Dr. Donnenfeld showed that initiating NSAID therapy 1 day before surgery is more effective than initiating the treatment on the day of surgery. Additionally, beginning treatment with NSAIDs 3 days preoperatively has been shown to be superior to their initiation 1 day before surgery.2 Therefore, I recommend that patients undergoing cataract surgery use NSAIDs for 3 days preoperatively except in high-risk patients such as those with epiretinal membranes, those who are more prone to developing CME, those with a history of uveitis or iritis, and those with diabetes. I direct such high-risk patients to take NSAIDs four times a day, starting 1 week preoperatively.

When treating high-risk patients, as defined earlier, I combine NSAIDs with steroids and start both 1 week before surgery. For the prevention of CME, I will continue the NSAIDs and steroids for 6 to 12 weeks. In combination, these two agents give my patients the best likelihood of a great outcome.

DISCONTINUING NSAIDs
If the primary reason for using NSAIDs is to combat corneal pain, they should be discontinued between 1 day and 1 week postoperatively. If the surgeon’s main goal of NSAID treatment is to prevent postoperative inflammation in the anterior chamber, then the drugs should be stopped at 1 or 2 weeks postoperatively. When used as prophylaxis for CME, NSAIDs should be continued for 4 to 6 weeks after surgery.

INNOVATIONS IN NSAIDs
Some of the newer NSAIDs like Acuvail (ketorolac 0.45%; Allergan, Inc.), Xibrom (bromfenac 0.09%; Ista Pharmaceuticals), and Nevanac (nepafenac 0.1%; Alcon Laboratories, Inc.) penetrate the eye better and have a longer duration of action. This is due to a carboxymethyl cellulose vehicle that acts as a carrier to protect the cornea and provides improved contact time of the NSAID with the cornea, which allows for less frequent dosing and improved visual acuity.⁵ These agents are also associated with less retinal burning and stinging than older formulations, which generally improves patients’ compliance and satisfaction.

CONCLUSION
The era of refractive cataract surgery has come of age. We no longer rely on patients’ vision testing, looking at dark letters on a white chart. Real-world testing and quality of vision are much more important indicators of successful outcomes. Using NSAIDs has proven to be effective at reducing or preventing retinal thickening from developing. Even though retinal thickening may be temporary in some cases, patients are often left with a permanent decrease in contrast sensitivity. It is therefore best to prevent the thickening if possible. Modern NSAID agents—especially with less frequent dosing—may improve compliance and further improve the ability of all physicians to add the use of NSAIDs to their pre- and postoperative regimens.

Kerry D. Solomon, MD, is director, Carolina Eyecare Research Institute, Mt. Pleasant, South Carolina, and adjunct clinical professor of ophthalmology at the Medical University of South Carolina in Charleston. He is a consultant to Alcon Laboratories, Inc., and Allergan, Inc. Dr. Solomon may be reached at (843) 881-3937; kerry.solomon@carolinaeyecare.com.

1. Wittpenn JR,Silverstein S,Heier J,et al.A randomized,masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients.Am J Ophthalmol.2008;146(4):554-560.
2. Donnenfeld ED,Perry HD,Wittpenn JR,et al.Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve.J Cataract Refract Surg.2006;32:1474 –1482.
3. Sandoval HP,De Castro LE,Vroman DT,Solomon KD.Evaluation of 0.4% ketorolac tromethamine ophthalmic solution versus 0.5% ketorolac tromethamine ophthalmic solution after phacoemulsification and intraocular lens implantation. J Ocul Pharmacol Ther.2006;22:251-257.
4. Cagini C,Fiore T,Iaccheri B,et al. Macular thickness measured by optical coherence tomography in a healthy population before and after uncomplicated cataract phacoemulsification surgery. Curr Eye Res.2009;34:1036-1041.
5. Donnenfeld E,Nichamin L,Hardten D,et al.Best-corrected visual acuity following treatment with twice-daily,preservative- free Ketorolac 0.45% in patients undergoing cataract surgery.Paper presented at American Society of Cataract and Refractive Surgery 2009 Annual Meeting;April 3-8,2009;San Francisco,CA.