While intracameral antibiotics may decrease endophthalmitis, some question necessity

The ESCRS endophthalmitis study showed their efficacy, but is the additional risk worth the benefit? Two physicians state opposing opinions.

Eric D. Donnenfeld

Recent studies have shown that intracameral injections of antibiotics during cataract surgery reduced the incidence of postoperative endophthalmitis. Despite this evidence and even though many surgeons have adopted this practice, some are skeptical that it is necessary. They cite the increased risk of using a compounded drug for an unapproved indication.

Eric D. Donnenfeld, MD, and Randall J. Olson, MD, discussed their opposing viewpoints regarding this prophylactic measure in separate interviews with Ocular Surgery News.

“The reason I went to intracameral antibiotics was that it just made sense to me to put the antibiotic directly at the site of potential infection,” Dr. Donnenfeld explained.

Dr. Olson said he understands that point but is not yet convinced that intracameral injections offer an advantage over a good topical regimen.

“I recognize that it may be important, but I certainly have reservations,” he said. “I don’t think we’ve proven that that’s our best way to go, and I think there are reasons for caution.”

Taking extra measures

Dr. Donnenfeld adopted the practice of injecting antibiotics intracamerally about 5 years ago in an attempt to reduce the incidence of endophthalmitis. He said his switch was supported by the results of the endophthalmitis study sponsored by the European Society of Cataract and Refractive Surgeons.

“There have always been anecdotal case reports and uncontrolled clinical trials that have showed the efficacy of intracameral antibiotics. The European study, although there were some flaws, really showed a dramatic reduction in endophthalmitis” with use of intracameral cefuroxime, he said.

The study showed that the incidence of endophthalmitis in the group not receiving cefuroxime was almost five times higher than in the group that did receive the intracameral injection.

“I don’t want to say that this is a definitive study, but it’s pretty good evidence that the incidence of endophthalmitis reduces by fivefold,” Dr. Donnenfeld said. “That’s certainly a positive step in the right direction.”

Based on the study results, he said, he is changing his intracameral antibiotic of choice from vancomycin to cefuroxime.

Topical antibiotics are still “extraordinarily important,” Dr. Donnenfeld added, but he said intracameral application allows a combination of strengths.

“Intracameral antibiotics give you basically a mixing-and-matching opportunity to give topical antibiotics on the surface of the eye to sterilize the ocular surface and then to use complementary antibiotics inside of the eye to kill any organism that enters the eye,” he said.

Dr. Donnenfeld said his surgical center previously saw around 10 cases of endophthalmitis in the approximately 8,000 cataract surgeries performed there per year. When he adopted use of intracameral vancomycin, that number was reduced to three or four cases, and with the combination of intracameral vancomycin and topical gatifloxacin, the rate dropped to one or two.

“The use of intracameral antibiotics and the use of fourth-generation fluoroquinolones have both been important in reducing our endophthalmitis,” he said.

Dr. Donnenfeld said intracameral antibiotics are especially important in patients with vitreous loss and, therefore, an increased risk of postop endophthalmitis. In other situations, such as patients with Fuchs’ dystrophy, inflammation, allergies or reduced endothelial cell counts, he avoids using them.

“You have to weigh the potential benefits vs. the risk,” Dr. Donnenfeld said. “The potential benefits are that it may decrease endophthalmitis. The risk is that it could result in toxic anterior segment syndrome.”

Unintended consequences

Dr. Olson said he has chosen not to use intracameral injections until they are further shown to have an advantage.

Randall J. Olson

“I’m a big believer in the law of unintended consequences — that is, that it’s not what you think of as a complication that ends up burning you, it’s what you often don’t realize is a complication,” he said.

Dr. Olson said he does not believe there is an endophthalmitis problem in his center, and he is reluctant to introduce new techniques that may cause other problems.

“It’s an unapproved use, and there’s always the risk of dilution errors and complication errors,” he said. “I’m a big believer in keeping it simple.”

While the ESCRS study showed an advantage for intracameral over topical antibiotics, he said, the study did not call for use of topical antibiotics until 1 day postoperative.

Dr. Olson begins topical treatment before surgery with a latest-generation fluoroquinolone four times a day 2 days before surgery and again directly after surgery, putting three or four drops in at the end of the surgery and then every 2 hours while the patient is awake.

He said a multivariate prospective study at his institution by Wallin et al has shown that this regimen resulted in a greater decrease of endophthalmitis as compared to topical drops started the day after surgery than with intracameral injections in the ESCRS study.

“If you wait until the next day to start antibiotics,” he said, “vs. giving them frequently the day of surgery, the risk of endophthalmitis went up almost 13-fold in our study.”

Dr. Olson also expressed concern that there is no ready-made intracameral preparation available. He said the use of a compounding pharmacy allows greater opportunity for error. If error occurs and a patient’s eyes are damaged, the physician could face legal ramifications due to the off-label nature of the treatment.

“If the incidence as a problem is very low, which it is in this case,” he said, “then the problem you’re solving or hoping to solve may not be as much as the problem you’re creating.”

Until there is further evidence of the superiority of intracameral injection, Dr. Olson said he will stay with his current regimen.

“Don’t add anything you can’t show is an advantage,” he said. “To me, all of the TASS cases we’ve followed over the years prove the law of unintended consequences. Furthermore, I am aware of at least one disastrous outbreak of TASS in association with prepared intracameral antibiotics.”

More studies needed

Both surgeons, despite their differing viewpoints, said there is a need for further studies. Dr. Olson suggested a study comparing his topical antibiotic dosing regimen to intracameral injections, and Dr. Donnenfeld called for further safety and efficacy trials for various drug candidates for intracameral use.

“I think it’s an area that deserves further scrutiny,” Dr. Olson said. “If indeed there is an advantage of the intracameral over frequent topical drops the day of surgery, then I’ll be the first one to say let’s do it.”

“It would seem to me that it wouldn’t be that hard to answer this definitively,” Dr. Olson said. “I’d like to see a drug company step up with a preparation that we can depend upon, that we don’t have to worry about the potential for stupid mistakes; just a simple dilution error and you’ve got something that’s toxic.”

Dr. Donnenfeld suggested that physicians who want to use intracameral antibiotics use vancomycin or cefuroxime, which have shown efficacy and have a long history of use.

“I think that the most important thing that I would suggest is that we need safety and controlled efficacy studies,” he said. “Rather than jump on the bandwagon and do something that hasn’t been thoroughly investigated, really stay with the antibiotics that either have a long history or have preferably peer-review literature to support their use.”

Dr. Olson suggested that if physicians choose to use this type of regimen, they should prepare the intracameral dose from drugs formulated for intravenous use rather than a topical solution.

For more information:

• Eric D. Donnenfeld, MD, can be reached at Ryan Medical Arts Building, 2000 North Village Ave., Rockville Centre, NY 11570 U.S.A.; +1-516-766-2519; e-mail: eddoph@aol.com.
• Randall J. Olson, MD, can be reached at John Moran Eye Center, 50 N. Medical Drive, Salt Lake City, UT 84132 U.S.A.; +1-801-585-6622; e-mail: randall.olson@hsc.utah.edu.

Reference:

• Wallin T, Parker J, et al. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract Refract Surg. 2005;31(4):735-741.

• Katrina Altersitz is the Managing Editor of Ocular Surgery News Latin America and India Editions.