Cataract surgeons continue to live somewhat dangerously in their efforts to prevent the rare but dangerous infection of post-op endophthalmitis. Topical prophylaxis remains the community standard of care, but an ever-growing number of surgeons feel intracameral injections of antibiotics are more effective. But while that method has largely been embraced in Europe, it presents a dilemma for U.S. ophthalmologists.
Intracameral injections still aren't FDA-approved and don't appear likely to be any time soon so their off-label use at this time could violate community standards of care. In addition, pharmaceutical companies have shown little interest in providing single-use, sterile intracameral antibiotics, so the drugs must be compounded. All this leaves eye surgeons at a crossroads where using superior post-cataract infection prevention potentially exposes them to medical and legal risk.
It all began with an oft-cited 2007 European Society of Cataract & Refractive Surgery (ESCRS) study that described the effectiveness of intracameral injection of a second-generation cephalosporin known generically as cefuroxime, 1 of the 3 prominent fourth-generation fluoroquinolone intracameral antibiotics (moxifloxacin and vancomycin are the others). That landmark study documented a 5-fold decrease in endophthalmitis rates, and many surgeons took notice.
"There's not much debate or controversy," says Kevin M. Miller, MD, Kolokotrones Chair in Ophthalmology at the David Geffen School of Medicine at UCLA. "The evidence is clearly in favor of injecting antibiotics. The literature is overwhelming."
Here's what you need to know about intracameral injections.
1. It's still not the standard of care. Because the FDA hasn't approved intracameral injections for cataract surgeries, the antibiotics are being used off-label. If your patient contracts an infection after an intracameral injection and sues you, "you'll be held against the community standard of care" what other local doctors use, says Dr. Miller. If most of them aren't administering intracameral injections, you might be open to liability.
Interestingly, many doctors feel compelled to use topical drops, even though they're also off-label and their effectiveness is questionable. "There's never been a study that shows that applying antibiotic drops to the eye after surgery reduces the rate of endophthalmitis," says Dr. Miller. "But because it's so common, it's now the community standard of care. So everybody does it, and if you don't, you're an outlier."
Until the FDA approves intracameral injections, the situation is unlikely to change. A new U.S. study in development, dubbed TIME ("topical versus intracameral moxifloxacin for endophthalmitis prophylaxis"), seeks to prove intracameral efficacy and safety at around 100 participating sites and, if so, secure FDA approval. Currently it's in the planning phase and seeking funding from a combination of federal and pharmaceutical industry sources, says Douglas Rhee, MD, chair of the Department of Ophthalmology & Visual Sciences at Case Western Reserve University in Cleveland, Ohio. Dr. Rhee, who is leading the study, isn't one of the growing number of U.S. surgeons roughly 45%, per an ASCRS survey who performs intracameral injections.
"I have been happy with my regimen of post-operative topical," he says. "Actually, I think it makes me a perfect person to study this, because there's the important concept of equipoise, which means you have to truly believe that either option could be good and that either option could win out."
2. There's still no single-use product. Just why is the FDA so reluctant to approve a treatment that's accepted practice elsewhere? For starters, Dr. Miller says the FDA's stringent protocol requirements for clinical trials and studies are difficult to achieve in this case because endophthalmitis is so rare. Secondly, adds Dr. Miller, what incentive is there for a pharmaceutical company to get a product on the market that might sell for $25 a vial and cannibalize sales of already successful antibiotic prophylactics?
3. Intracameral antibiotics must be compounded. You must rely on a compounding pharmacy to prepare intracameral injections. "You have to trust the pharmacy to mix it properly and not contaminate it," says Dr. Miller. "That's what scares a lot of people from using intracamerals: the incompetence of the source."
Among the potential problems from poor compounding are the inadvertent presence of preservatives, overdosing that can lead to complications like retinal ischemia and macular edema, and the possibility of toxic anterior segment syndrome (TASS) or toxic posterior segment syndrome (TPSS).
4. There are 3 intracameral antibiotics. There's cefuroxime, vancomycin and moxifloxacin. Cefuroxime is widely used in Europe, but its weaknesses have become apparent to some. "It has high resistance and a lot of organisms aren't fazed by it," says Dr. Miller; the most prominent of those, perhaps, is methicillin-resistant Staphylococcus aureus (MRSA). In the U.S., cefuroxime is approved and labeled only for intravenous and intramuscular use. Compounding it is a complicated, laborious process. In Europe, those concerns have been eliminated with the introduction of a premixed, single-use formulation, Aprokam, made specifically for intracameral application. The U.S. isn't so lucky.