Although corticosteroids are commonly prescribed after cataract surgery, they may not be necessary. The new topical NSAIDs are at least as potent, safer, and require less frequent dosing.
Ocular inflammation after cataract surgery is characterized by pain, redness, and often by some temporary loss of visual acuity. Beyond the immediate discomfort to the patient, however, is the more significant danger that the inflammation may produce permanent vision loss as a result of cystoid macular edema (CME).1 Typically seen 3 to 4 weeks after surgery, CME results from the release of prostaglandins by damaged tissue.
In cataract surgery, most of the damage is from prostaglandin release in the anterior chamber, which may seep into the posterior segment, sparking inflammation there. With improvements in surgical instruments and techniques, today’s cataract surgery rarely creates such direct insult to the posterior segment. However, if the inflammation in the front of the eye can be controlled following surgery, there is nearly zero chance of significant inflammation developing in the back of the eye.
Topical corticosteroids and topical nonsteroidal antiinflammatory drugs (NSAIDs) are the two main options at surgeons’ disposal for controlling postoperative ocular inflammation. While both drug classes decrease inflammation, they have different properties and different mechanisms of action.
Steroids block the inflammatory cascade at an early stage: the arachidonic acid pathway activated by tissue damage. But to be effective, steroids need to pass through cell membranes and enter the nucleus, which is limited because of their lipophobic nature. In addition, steroid side effects include intraocular pressure (IOP) elevation, delayed wound healing, and increased susceptibility to infection.
NSAIDs block cyclooxygenase (COX-1 and COX-2), enzymes that convert arachidonic acid into the prostaglandins that directly mediate inflammation. NSAIDs enter cells readily and effectively shut down prostaglandin formation; within its class, the brominated NSAID bromfenac penetrates cells particularly well. The traditional caution with ocular NSAIDs is that some have been associated with punctate epithelial keratitis and even corneal melt, although the latter has been very rare since the 1990s.2
Steroid Plus NSAID?
Most often, an NSAID is prescribed in conjunction with a topical steroid, but whether steroids and NSAIDs truly act synergistically has been controversial. Some older studies reported that the addition of a weak NSAID improved the effects of treatment with a weak steroid. However, those findings might be explained simply from the suboptimal dosing of either drug. The mechanisms of action suggest that a strong NSAID and a strong steroid should have a similar, non-additive effect, since both are blocking the same pathway, albeit at different places. Indeed, recent studies have found that the newer and stronger NSAIDs, such as bromfenac, are at least as effective as topical steroids for treating inflammation.3,4
These findings raise the question: which class of drug to use following surgery? In my clinical practice the question arose as a very practical matter a few years ago, when the provision of free topical steroids in cataract kits was stopped. Since we knew we would need to write prescriptions for all antiinflammatory medications, we decided to prescribe bromfenac on the theory that it was less expensive overall, and that a topical steroid could be added later if necessary. After a few months, it was clear that we had not had any occasion to prescribe a steroid. At that point we began a retrospective study in our clinic comparing the outcomes following bromfenac (Bromday®; Bausch + Lomb) administration with those following prednisolone (Pred Forte®; Allergan) in the setting of cataract surgery.5
We reviewed 442 eyes, 225 treated with bromfenac and 217 treated with prednisolone. Patients operated on between January and August 2010 had been treated with prednisolone beginning on postoperative day 1, with tapering after 3 to 4 weeks. Patients operated on from September 2010 to May 2011 were prescribed bromfenac beginning on preoperative day 2 and continuing until the bottle was exhausted (about 4 weeks). Antibiotics (gatifloxacin and azithromycin) were started at the same time as the antiinflammatory and were continued for 1 week after surgery.
In this retrospective consecutive case review, we included eyes with floppy irises, diabetes, very hard nuclei, and 4+ cataracts—no eye was excluded for any medical reason. Eyes were excluded only for inadequate follow-up data. After exclusions, there were 200 eyes in each group. Outcomes examined included inflammation at the 2- and 4-week follow-up visits, presence of CME at 1 month, postoperative IOP elevation (defined as an increase in measured IOP > 5 mm Hg from the patient’s baseline IOP at either the 2- or 4-week visit) and best corrected visual acuity (BCVA) at 1 month.
At 2 weeks, 12% of eyes in the bromfenac group had some inflammation (trace cell or greater), not significantly different from the 8% of eyes in the prednisolone group. At 4 weeks, the occurrence of inflammation fell to 1.5% and 2% of eyes in the bromfenac and prednisolone groups, respectively. CME was seen in one eye in the bromfenac group and two eyes in the prednisolone group. (Patients in the steroid group who were at risk of CME [about 20% of the total] were also administered an NSAID.) Mean BCVA was 20/27.2 in the bromfenac group and 20/26.6 in the prednisolone group, a difference that was not significant.
The only difference of importance between the treatment groups was in the rate of IOP elevation. We defined elevated IOP as 5 mm Hg above baseline, a level that is significant but treatable. Of all eyes treated with bromfenac, 7 (3.5%) were seen to have an IOP elevation at 4 weeks, compared to 16 (8%) in the prednisolone group (P = .08). When the eyes that had retained lens fragments (a common correlate of IOP elevation) were excluded, the rate of IOP elevation in the bromfenac group dropped to 2.5%, while remaining at 8% in the prednisolone group (P = .02). When all the eyes with a history of glaucoma—the highest-risk eyes—were examined, 32% (8 of 25 eyes) in the prednisolone group showed an elevation in IOP. By contrast, none of the 17 glaucomatous eyes in the bromfenac group showed any IOP elevation.
There are other advantages to prescribing an NSAID in place of a steroid. When using Bromday, patients need only remember their eye drops twice a day: one drop of Bromday and one of antibiotic in the morning, and then antibiotic alone in the evening for the first week. After that, patients instill just one drop of Bromday each day until the bottle is exhausted. This is much simpler than the tapered schedule with steroids: 4 times a day for 2 weeks, then 3 times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week. Understandably, patients always had difficulty remembering and/or complying with this regimen.
Simplification of the drug regimen after surgery will also save many patients money. Patients with good insurance are less concerned with the actual cost of the drug than with the number of copays they have to make. Assuming the patient will have both eyes operated on within a matter of weeks, we prescribe a twin-pack of Bromday along with a prescription for gatifloxacin (Zymaxid®; Allergan). Each bottle of Bromday will cover one eye; the Zymaxid is enough for both eyes, and so we tell the patient to save the bottle for the second surgery. This way, patients have only two copays, rather than four or more under the previous regimen, and they are appreciative.
Overall, the data from our clinic and elsewhere indicates that a topical NSAID is at least as effective as a topical steroid for treating inflammation following cataract surgery, and probably safer. At our clinic, we have no intention of going back to using steroids for routine surgeries.
On the other hand, it is my impression that most physicians still prefer to prescribe steroids. We suggest that experience can be gained with the NSAID-only regimen by prescribing it first for the patients at high risk of IOP elevation, or consider using a low-risk steroid like loteprednol etabonate (Lotemax® Bausch + Lomb). Ultimately, we think ophthalmology will follow the lead of other surgical specialties, such as orthopedics, where steroids are no longer prescribed following surgery; and the potential problems of tapering, healing delay, and IOP rise will be avoided.
THE BOTTOM LINE
Topical corticosteroids after cataract surgery can be replaced with topical NSAIDs without any loss of antiinflammatory activity and with potential gains in safety. Once-daily dosing and the lack of tapering are major advantages for patient convenience and compliance; and in many cases patient costs can be reduced.
Keith Walter, MD, is assistant professor of surgical sciences–ophthalmology at Wake Forest University Eye Center, Winston-Salem, NC. He is a consultant for Bausch + Lomb and Alcon. Freelance writer Zaid Smith, PhD, assisted in the preparation of this article.
1. Lobo C. Pseudophakic cystoid macular edema. Ophthalmologica. 2012;227(2):61-7.
2. Singer M, Cid MD, Luth J, et al. Incidence of corneal melt in clinical practice: our experience vs. a meta-analysis of the literature. J Clinic Experiment Ophthal. 2012. Available at: http://www.omicsonline.org/2155-9570/2155-9570-S1-003.pdf?aid=3927.
3. Endo N, Kato S, Haruyama K, Shoji M, Kitano S. Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes. Acta Ophthalmologica. Dec 2010;88(8):896-900.
4. Miyake K, Ota I, Miyake G, Numaga J. Nepafenac 0.1% versus fluorometholone 0.1% for preventing cystoid macular edema after cataract surgery. J Cataract Refract Surg. Sep 2011;37(9):1581-8.
5. Walter K, Estes A, Watson S, Ellingboe M. Management of ocular inflammation following routine cataract surgery—topical corticosteroid (prednisolone) versus topical non-steroidal (bromfenac). US Ophthalmic Review. 2011;4(2):97-100.