January 2015




Intracameral antibiotics

Intracameral antibiotics versus topical

by Maxine Lipner EyeWorld Senior Contributing Writer


I think that surgeons want to use [intracameral antibiotics], and the number using them is rising. But if [surgeons are] using them they need the protection of an approved product, particularly when an approved product [Aprokam] actually exists. Peter Barry, MD


To stave off endophthalmitis cases such as this one, many are weighing the evidence on whether an intracameral approach is better than a topical one.

Source: Francis Mah, MD

Best practices: What is the evidence?

For practitioners performing cataract surgery, keeping endophthalmitis at bay is on everyones mind. However, while some swear by intracameral antibiotics, others continue using the topical approach. EyeWorld is honing in on just what the scientific evidence supports.

Audrey Talley Rostov, MD, Northwest Eye Surgeons, Seattle, thinks the evidence clearly shows that the intracameral approach is superior. She views the ESCRS prospective, randomized study, published in March 2006 in the Journal of Cataract & Refractive Surgery (JCRS), as a landmark trial.1 Patients in the study were placed in one of 4 groups to receive topical medication, intracameral antibiotics, both antibiotics, or no antibiotics. With the intracameral approach, patients had a 5-fold decrease in endophthalmitis, she said. Meanwhile, the first large-scale U.S. study, conducted by Neal Shorstein, MD, and published in the January 2013 issue of JCRS, also favored the intracameral approach, she said.2 There was a 2.2-fold decline in endophthalmitis during the first 2 years of the 5-year retrospective study following the introduction of intracameral cefuroxime, she said. A further 10-fold decrease was observed during the next 2 years of the study when all patients received either intracameral cefuroxime, moxifloxacin, or vancomycin. Likewise, Peter Barry, MD, consultant, Royal Victoria Eye and Ear Hospital, and St. Vincents University Hospital, Dublin, is convinced that the intracameral method is superior in staving off endophthalmitis. He also views the ESCRS study, in which he was lead author, as a pivotal one. While a concern with the study was that the background rate of endophthalmitis was too high, Dr. Barry argues that this is not so. The Shorstein study from northern California last year had a 0.35% rate that they were running when they decided to switch to the intracameral route, which is exactly the same as the control group in the ESCRS study, he said. In addition, a Swedish national study, which was also published in the January 2013 issue of JCRS, looked at 1 million consecutive patients in their database.3 In this study endophthalmitis rates rose to the 0.3% mark without the intracameral antibiotics, Dr. Barry said.

European preference

In Europe, many physicians are convinced that the intracameral approach is the way to go based on the evidence of the studies, even beyond the landmark ESCRS trial, Dr. Barry said. There have been many studies done in France and Spain where institutions have made the decision to switch and have recorded their results, he said. In every study you read from Europe or elsewhere around the world where the intracameral approach was adopted, when endophthalmitis rates were high, they got very low and when they were low they got even lower, Dr. Barry said.

He credits the ESCRS trial with spurring additional work in the area, which ultimately led to a change in European practice patterns. I think it would be wrong to give the ESCRS study entire credit, but I think that it was the overwhelming driving force, and it resulted in a large volume of studies being conducted in Spain, France, and other European countries, Dr. Barry said. However, the Swedes used the intracameral approach before anyone else. I think that Per Montan and coworkers at St. Eriks in Stockholm are the father figures of intracameral antibiotic prophylaxis,4 he said, adding that Spanish ophthalmologists, who started a survey of the use of intracameral cefazolin back in 2002, also had an important role in this.

Currently the only intracameral drug for which there is an evidence base is intracameral cefuroxime, Dr. Barry said. The French product Aprokam (cefuroxime, Thea Group, Clermont-Ferrand, France) is approved by the European Medicines Agency, he noted. In a recent ESCRS survey published in the January 2014 issue of JCRS, which Dr. Barry authored, cefuroxime was the overwhelming choice.5 In Europe, of the 74% of people in the survey who use intracameral antibiotics, 82% of those use cefuroxime, Dr. Barry said. The number using vancomycin or moxifloxacin is fairly small.

Topical literature

In addition to the intracameral approach, the literature holds some support for topical antibiotics, said Francis Mah, MD, director of cornea and external disease, and co-director of refractive surgery, Scripps Clinic, La Jolla, Calif. There are retrospective studies showing efficacy of the topical antibiotic approach for cataract procedures that date back to 1964 with a study that involved more than 20,000 cases,6 he said.

Henry Allen showed that not using preoperative antibiotics was a significant risk factor for postoperative infections, Dr. Mah said. The same group in 1974 showed that switching an antibiotic can further reduce the rate of endophthalmitis retrospectively.7 More recently there have been several papers on the fluoroquinolones retrospectively showing that they have reduced the rate of endophthalmitis more and that by switching to a different fluoroquinolone you could potentially reduce the rate further, he said. In addition to the retrospective approach, many studies have considered how the patients own flora fares against antibiotics, Dr. Mah noted. Evidence with the use of povidone-iodine has shown that this was the origin of endophthalmitis in about 80% of cases. Some studies consider whether colonies survive once an antibiotic is applied. The only problem is that no one has ever prospectively shown that topical antibiotics actually correlate with a reduction in endophthalmitis, Dr. Mah said. I think that a lot of the evidence in the literature right now for topical is retrospective and surrogate evidence. To date, the only prospective trial that has been done using topical antibiotics was the ESCRS study, which compared this with the intracameral approach, Dr. Mah said. Their study showed that topical levofloxacin 0.5% did nothing in terms of reducing the rate of endophthalmitis, Dr. Mah said. He added that this older generation topical fluoroquinolone might not have been the best choice. Dr. Mah also raised the concern that the study might not have been large enough to find the difference. They had more than 16,000 patients, but if you have a rate of endophthalmitis of approximately 1 in 1,000, you need closer to 50,000 to 70,000 patients, he said. So there isnt any prospective evidence that topical antibiotics do in fact reduce endophthalmitis. However, this study did show that intracameral antibiotics reduce the rate of endophthalmitis, he said.

All in all, there have been 4 prospective studies showing that intracameral cefuroxime reduces the rate of endophthalmitis, Dr. Mah said. While he concedes that the support in the literature is much stronger for intracameral antibiotics, he thinks that before changing antibiotic protocols, practitioners should consider their own endophthalmitis rates. The literature pegs the average at about 1 in 1,000, with some papers putting the rate at 1 in 5,000. I think if youre at that 1 in 1,000 ratio or even better, thats pretty good, so I dont know that you necessarily have to change what youre doing, he said. Although Dr. Mah himself is a topical antibiotic user and noted that in 15 years, he has never had a case of endophthalmitis, he is currently transitioning to intracameral antibiotics. Having said that, Dr. Mah noted each surgeon must evaluate the data and their practice pattern. I dont see how I could push someone else to look at something that might potentially complicate surgery, he said. There might, for example, be concerns about TASS or anaphylaxis with intracameral medications in the U.S. where such medications must be compounded because there is no FDA-approved option. Meanwhile, Dr. Talley Rostov embraces the intracameral approach, which she started using years ago after experiencing just 1 endophthalmitis case. Initially she started using antibiotics in the bottle, but then moved on from this. I switched over from vancomycin in the bottle to the intracameral when the Shorstein article came out, Dr. Talley Rostov said. I routinely employ the use of intracameral antibiotics at the end of the case, then I still use topical antibiotics for a week following. She hopes that others in the U.S. follow suit based on the evidence. Going forward, Dr. Mah thinks that practice patterns in the U.S. will ultimately change because the literature supports intracameral antibiotics. Most people are looking for a single use, fool-proof method with the optimal medicationthe kind of FDA-approved method, he said. If that was available, the data are showing that in Europe 90% of people would seriously consider it, and in the U.S., almost 80% of surgeons would consider something like that. Dr. Barry likewise thinks it is inevitable that intracameral antibiotics will prevail in the U.S. I think that surgeons want to use them, and the number using them is rising, he said. But if [surgeons are] using them they need the protection of an approved product, particularly when an approved product [Aprokam] actually exists.

References Intracameral antibiotics article summary

1. Barry P, Seal DV, Gettinby G, et al. ESCRS Endophthalmitis Study Group. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: preliminary report of principal results from a European multicenter study. J Cataract Refract Surg. 2006;32: 40710.

2. Shorstein NH, Winthrop KL, Herrinton LJ. Decreased postoperative endophthalmitis rate after institution of intracameral antibiotics in a Northern California eye department. J Cataract Refract Surg. 2013; 39:814.

3. Friling E, Lundstrm M, Stenevi U, et al. Six-year incidence of endophthalmitis after cataract surgery: Swedish national study. J Cataract Refract Surg. 2013; 39:1521.

4. Wejde G, Montan P, Lundstrm M, et. Al. Endophthalmitis following cataract surgery in Sweden: national prospective survey 19992001. Acta Ophthalmologica Scandinavia. 2005; 83:710.

5. Barry P. Adoption of intracameral antibiotic prophylaxis of endophthalmitis following cataract surgery: update on the ESCRS Endophthalmitis Study. J Cataract Refract Surg. 2014; 40:13842. 6. Allen HF, Mangiaracine AB. Bacterial endophthalmitis after cataract extraction. A study of 22 infections in 20,000 operations. Archives of Ophthalmology. 1964; 72:4546. 7. Allen HF, Mangiaracine AB. Bacterial endophthalmitis after cataract extraction II. Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics. Archives of Ophthalmology. 1974;91:37.

Editors note: Dr. Barry has financial interests with Spectrum Thea (Newcastle, U.K.). Drs. Mah and Talley Rostov have no financial interests related to their comments.

Contact information

Barry: peterbarryfrcs@eircom.net
Mah: mah.francis@scrippshealth.org
Talley Rostov: atalleyrostov@nweyes.com

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Intracameral antibiotics versus topical Intracameral antibiotics versus topical
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