Article Date: 9/1/2006

CONTINUING MEDICAL EDUCATION
Where NSAID Therapy Begins

Follow the trail of possibilities, from the cataract surgeon's blade to your office.

Jeffrey S. Heier, MD: The goal of this discussion is to review advances in nonsteroidal anti-inflammatory drugs (NSAIDs). We will talk about how retinal specialists use NSAIDs today, particularly in the context of cystoid macular edema (CME). We want to consider how NSAIDs affect patient compliance, our ability to attack early manifestations of edema, and ultimately improve patient outcomes. I want to start our dialogue with some first-hand insights from Dr. Francis Mah, a cornea external disease and refractive surgery expert at the University of Pittsburgh.

Dr. Mah, how are you and other anterior segment specialists using NSAIDs for cataract surgery and perhaps other procedures that could involve retinal specialists in the management of follow-up care or complications?

PREVENTING INFLAMMATION

Francis S. Mah, MD: Most important is that we use NSAIDs to help prevent CME before we perform surgery. Studies have confirmed the benefits of treating CME with NSAIDs.1,2 Most ophthalmologists also believe using NSAIDs prophylactically can help patients a great deal.

Besides controlling inflammation, these agents create a mydriatic effect, preventing miosis during surgery. This is important because, as shown in numerous studies, smaller pupils are associated with increased risks of complications.3,4 In addition, NSAIDs control postoperative pain, which is paramount in meeting patients' increasingly high expectations. Of course, we also use NSAIDs for allergy, one of the original indications, as well as for traumatic pain, erosions and corneal abrasions.

A QUESTIONABLE PAST

Dr. Mah: Historically, the use of NSAIDs has followed an up-and-down course. From 1999 to 2000, reports of corneal melts were linked to generic diclofenac. At the time, the use of NSAIDs in cataract and refractive surgery was considered a safer alternative to corticosteroids. But once peer-reviewed reports raised concerns about corneal melts, many anterior segment surgeons quickly turned away from NSAIDs.5,6

Dr. Heier: One key issue for us is the poor outcome that typically results when prophylactic treatment is not used. I saw the effects of this situation first-hand when those corneal melts were reported. At the time, most of the 13 anterior segment surgeons in our practice stopped using NSAIDs. We saw a dra-
matic increase in the incidence of CME, and it was not reversed until they resumed using the NSAIDs.

Dr. Mah: We have reached an interesting juncture because, once again, we are describing the nonsteroidal as a safer, better therapeutic category that includes more potent options. How does all of this relate to the care that you, as retinal specialists, provide? I would say that it puts you in a position to help identify the best NSAIDs and the key issues involved in the treatment and prophylaxis of CME. Since CME patients often will come to your offices, you will end up understanding how these agents should be used. 

PRE-OP AND POST-OP USE

Seth Yoser, MD: Another important point is that physicians need to use NSAIDs preoperatively and postoperatively. Patients obviously have their own issues, ranging from a variety of disease states to high expectations. With these issues in mind, I recommend aggressive treatment before and after surgery for different at-risk groups, including patients with any of the following characteristics:

• History of inflammation in the fellow eye

• Diabetes without complete resolution of macular edema, following a laser treatment or triamcinolone acetonide (Kenalog)

• History of uveitis that has been poorly controlled

• History of viral keratitis.

These patients benefit from preoperative dosing of an NSAID 1, 2 or 3 days before surgery and for 2 to 3 weeks or more after surgery. This approach will keep their eyes as comfortable and least inflamed as possible.

EVIDENCE SUPPORTING PROPHYLAXIS

Dr. Heier: The advantages of prophylactic treatment have been addressed in numerous studies. Calvin Roberts, MD, and others have completed impressive studies showing that 3-day preoperative treatment provided greater blunting of postoperative effects than what was associated with 1-day preoperative treatment.7,8

Juan Orellana, MD: I have found this to be true in practice. Prophylaxis is essential because treating CME can be very challenging. Once CME begins, we may need to administer intravitreal triamcinolone acetonide, raising a host of additional risk factors. The patient is much better off if you do not have to remedy a preventable condition.

Dr. Mah: Eric D. Donnenfeld, MD, added to the earlier research done by Dr. Roberts, performing a prospective study that looked at dosing with NSAIDs 3 days, 1 day and 1 hour before cataract surgery.9 Dr. Donnenfeld focused on various parameters, including pupil size, at the start of surgery until intraocular lens implantation. He also looked at postoperative inflammation and used patient surveys to measure pain during and after surgery.

After reviewing his results, he found he could achieve statistically significant improvements in efficiency — as measured by reduced cost and time in the operating room — when he used 3 days instead of 1 day of prophylaxis. In turn, 1 day proved to be statistically better than 1 hour. Improved pupil size was also evident, again depending on the length of prophylaxis. This is convincing data that tells me I should be using preoperative NSAIDs at least 1 day, if not 3 days, before I perform cataract surgery.

Dr. Heier: Results such as these are important clinically. What was the primary reason for his improved efficiency?

Dr. Mah: Increased mydriasis and improved comfort for the patient, leading to fewer distractions for the surgeon.

A PREFERRED REGIMEN

Dr. Heier: Mindful of these new developments, what do retinal specialists need to know about cataract surgery today, Dr. Mah? Exactly what regimen are you using?

Dr. Mah: I treat with an NSAID about 3 days before cataract surgery in every patient, and 1 week before surgery if a patient is at high risk for developing complications. I am spending more time closely identifying high-risk candidates. On the day of surgery, I give all cataract surgery patients an NSAID, combined with an antibiotic.

Three to 4 hours after cataract surgery, I tell patients to begin administering their postoperative medications, including an antibiotic into the eye. Because I use topical anesthesia, I can use an antibiotic, an NSAID and a corticosteroid the same day as the surgery without causing complications or discomfort. That first day, I use a corticosteroid and an antibiotic every 2 hours, and I use the NSAID for several weeks post-op. For example, I can give bromfenac ophthalmic solution 0.09% (Xibrom) twice a day. Patients who are not at risk for complications and who are following a normal postoperative course can continue with this NSAID for about 4 to 6 weeks.

For high-risk patients, I continue the NSAID treatment for 3 months. The antibiotics are stopped in about a week, when the epithelium has healed. I taper the corticosteroid fairly rapidly, ending the treatment in 2 to 3 weeks.

Dr. Heier: Do you taper the NSAID?

Dr. Mah: No, we just stop the NSAID at the end of therapy.

BROADER INSIGHTS

Dr. Heier: These insights are very helpful to us. Under-standing the experience of anterior segment surgeons and identifying information they need from us will be important to maximize surgical patient outcomes.

REFERENCES

1.    McColgin AZ, Heier JS. Control of intraocular inflammation associated with cataract surgery. Curr Opin Ophthalmol. 2000;11:3-6.

2.    Heier JS, Topping TM, Baumann W, et al. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology. 2000;107:2034-2039.

3.    Lam PT, Poon BT, Wu WK, et al. Randomized clinical trial of the efficacy and safety of tropicamide and phenylephrine in preoperative mydriasis for phacoemulsification. Clin Experiment Ophthalmol. 2003;31:52-56.

4.    Peternel V, Findl O, Kruger A, et al. Effect of tropicamide on aqueous flare before and after cataract surgery. J Cataract Refract Surg. 2000;26:382-385.

5.    Flach AJ. Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Trans Am Ophthalmol Soc. 2001;99:205-212.

6.    Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf. 2002;25:233-250.

7.    Goguen ER, Roberts CW. Topical NSAIDS to control pain in clear corneal cataract extraction. Insight. 2004;29:10-11.

8.    Price MO, Price FW. Efficacy of topical ketorolac tromethamine 0.4% for control of pain or discomfort associated with cataract surgery. Curr Med Res Opin. 2004;20:2015-2019.

9.    Donnenfeld E. NSAIDs as a Surgical Tool. Presented at the American Society of Cataract and Refractice Surgery, April 15-20, 2006, Washington, DC.



Retinal Physician, Issue: September 2006