Improving Cataract Postop Therapy

New options simplify care, but generic NSAIDs raise concerns.

Antibiotics, steroids and NSAIDs are workhorse drugs for cataract surgeons in the immediate postoperative phase. Originally, all needed to be given QID—in fact, for the last four decades, an antibiotic and steroid QID has been the standard for cataract surgery drops. More recently, the improved potency of these medications has enabled surgeons to reduce dosage to once or twice a day. The duration of both the steroids and the antibiotic has meant a decrease in length of use, often to less than two weeks. Here's an overview of recent changes in cataract surgery medications and the patients/situations for which they are best suited.

Enhancements Simplify Dosing

Over the last 30 years, NSAIDs gained acceptance as a QID medication that helped with multiple aspects of cataract surgery. Topical NSAIDs have a very broad utility throughout ophthalmology: They are approved and/or widely used off-label for preventing intraoperative miosis, reduction of pain and inflammation following cataract surgery, reduction of pain following refractive surgery, prevention and treatment of cystoid macular edema, treatment of seasonal allergic conjunctivitis, induction of cyclosporine therapy for dry eye—the list goes on and on. For the past 20 years, I have used an NSAID on all my cataract cases except when a new generic NSAID was introduced briefly with subsequent corneal melts and was pulled from the market. During this period of no NSAID availability, many surgeons saw a spike in our CME post-cataract surgery.

The addition of bromfenac (Xibrom and Bromday, Ista Pharmaceuticals) allowed many of us to rethink QID dosing. First, Xibrom demonstrated that a twice-daily medication can be very effective at controlling pain, keeping the pupil dilated and preventing postop inflammation and CME. Second, recent studies convinced the FDA to approve bromfenac for use once a day. Patients really enjoyed the decreased dosing.

The introduction of both stronger steroids and antibiotics in the last three years has allowed further reduction of therapy around the time of cataract surgery without increased risk of infection or late inflammation.

High-potency difluprednate (Durezol, Alcon) has been used BID with good results in patients who do not have glaucoma concerns. Its frequency and duration can be increased for those patients with higher risk of inflammation. Loteprednol etabonate (Lotemax, B+L) is well tolerated in glaucoma patients or known steroid responders; in these cases, I use it QID and taper over four weeks.

Three different fourth-generation fluoroquinolones have all been proven useful. A higher concentration gatifloxacin (Zymaxid, Allergan) has helped with BID dosing; preservative-free moxifloxacin (Vigamox, Alcon) has been safely used in the eye immediately after cataract surgery; and I have used besifloxacin (Besivance, Bausch + Lomb), with its DuraSite component, before and after surgery to help with both lid issues and postoperative anti-infection.

The Generics Issue

Most ophthalmologists continue to use an NSAID preop for several days and for at least four weeks postop. The new NSAID Bromday's once-daily dosing is very convenient for this medication class that is used for much longer duration.

Because of this wide use, it would seem a boon to our patients (or at least their wallets) to have generic versions of our favorite NSAIDs available. However, both history and recent experience suggest that ophthalmologists should avoid generic NSAIDs, or at least be very circumspect in adopting them. Cutting corners on postop medications to save a few dollars is worse than being penny-wise and pound foolish. It's simply bad medicine.

The availability of new generics is a measure of the success of the NSAID class. We began our clinical relationship with NSAIDs decades ago with flurbiprofen (Ocufen, Allergan), diclofenac (Voltaren, Novartis), and ketorolac tromethamine (Acular, Allergan). Acular LS replaced Acular and then came Xibrom, nepafenac (Nevanac, Alcon), Acuvail (Allergan), and, most recently Bromday. Innovation has continued, with potency and tissue penetration improving, dosing frequency decreasing and comfort increasing. We are fortunate to have continued vibrancy in product development, giving us a choice of several brand medications and several generics. In other drug classes, particularly systemic medications, generics have provided substantial economic benefits and tangible patient savings.

Unfortunately, the promised value of generic NSAIDs in ophthalmology has been consistently undercut by performance problems, adverse events, confusing or illegal substitution and weak economic benefits. These downsides are not restricted to the well-documented problems with generic diclofenac but have also arisen with more recent entrees.

► Cases of ulcerative keratitis, corneal melts, etc., with generic diclofenac were well documented with ASCRS in the last two decades and caused withdrawal of all NSAID drops for a brief period. During this period, the CME rate went up significantly in my practice and returned to normal when NSAIDs where put back on the market.

► Recent anecdotal reports of SPK with generic ketorolac [15-25%]; two- to three-line drop in acuity following surgery; rebound inflammation (personal communication, Wittpenn and Trattler); other corneal issues such as melts reported by Uday Degan are beginning to be seen on chat lines. I have seen SPK in my own patients who received a generic substitute for Bromday without my permission.

► Concern about uneven quality of generics/between generic manufacturers has been discussed at our meetings.

► Dosing confusion for patients going from once or twice a day to QID because of a generic switch is often an issue in my practice.

► Incorrect or illegal therapeutic substitution (ketorolac for Bromday or bromfenac for Bromday).

► The value myth: Generics aren't that much cheaper, particularly than brands with good formulary position. I have seen patients pay only $10 less for a generic medication when in fact with a manufacture's coupon they could have paid for the branded drug and saved $40.

► Short and long-term cost to the practice of call-backs, unscheduled post-op visits, etc. As they say, “The case can go well but then the patients come back with a problem resulting from the eye drops and they blame the surgeon.”

Recently in my practice, a bilateral premium IOL patient was switched by the pharmacist from my once-a-day branded NSAID to generic QID ketorolac. Because of stinging, the patient discontinued his medication after less than a week—without informing the practice of either development. Further, the patient's history was complicated slightly with diabetes. Though his vision was great the first two weeks postop, over the next three weeks his vision decreased dramatically. The patient came in at five weeks with marked DME and CME with vision of 20/100 OU (Figures 1 and 2). The patient was started on Bromday. Three weeks later vision was back to 20/30 and he could drive without difficulty.

Figure 1. Corneal toxicity from generic bromfenac, 10 days postop.

Figure 2. Cystoid macular edema/DME. Patient switched from QD NSAID to generic QID ketorolac. After two weeks, the patient's vision began to drop dramatically. At five weeks, the patient came in with marked DME/CME with vision 20/100 OU.

New Era of Cataract Surgery

With premium IOLs and the advent of femto-phaco, our surgical outcomes are continuing to get better and better. Our patients' expectations are rising in concert. Today, patients assume cataract surgery will be fast, painless and problem-free, with a stellar visual outcome right away—particularly if they've paid for a premium IOL. Their experiences carry beyond their friends and family as they use social media to critique our practices.

Surgeons need to educate patients about the value of the medicines they are prescribed and that the role they play is just as important to the visual outcome as the surgical technique, instrumentation and IOL. If they understand this, few patients would roll the dice by ignoring our recommended dosing or changing their medication. For those who still opt for a generic or can't afford a brand name, we are well advised to be vigilant about potential problems. OM

Dr. Katsev is in private practice in Santa Barbara, CA. Contact him at Katsev@aol.com.