May 2007

 

CATARACT/ IOL

 

Perspectives in lens and IOL surgery

The ESCRS endophthalmitis study—

implications for now and the future

 


by Peter Barry, F.R.C.S.
 

There is no more pressing, or controversial, issue in ophthalmology today than post-cataract surgery infectious endophthalmitis. The literature is contradictory with respect to many of the considerations involving prophylaxis, surgical technique, antibiotic regimen, and other issues surrounding endophthalmitis that are familiar to all cataract surgeons. The European Society of Cataract and Refractive Surgery (ESCRS) made a major commitment, several years ago, to study methods for prevention of endophthalmitis. This month’s article by Peter Barry, F.R.C.S., who led the ESCRS endophthalmitis study and presented it at the ESCRS symposium in Portugal last year, details the results of that study and the lesson’s learned. All cataract surgeons will benefit from any information that can improve our surgical protocols, techniques, devices, and practices. Dr. Barry is a leading ophthalmologist with a scope of international activities. He is most well-known to all for his leadership role in the European Society of Cataract and Refractive Surgery over the past decade.

I. Howard Fine, MD, Column Editor

 

Definitive study results indicate the prevention of endophthalmitis an achievable goal

The ESCRS study on antibiotic prophylaxis of endophthalmitis following phaco emulsification cataract surgery was designed to determine whether intracameral Ceftin (cefuroxime, Glaxo SmithKline, United Kingdom) at the end of the surgery and/or intensive peri-operative Levaquin (levofloxacin, OrthoMcNeil, Raritan, N.J.; in Europe, marketed as Tavanic by Sanofi Aventis, Paris) drops reduced the incidence of acute post-op endophthalmitis.1, 2, 3

Study design

For ethical reasons, there could not be a true control group with no prophylaxis whatsoever. Therefore, each patient in every group received pre-op Betadine (povidone iodine, Purdue Pharmaceuticals, Stamford, Conn.), the only prophylaxis for which there is an evidence base, and were instructed to take topical levofloxacin drops four times a day (q.i.d.) for a week, commencing on day one post-op to prevent wound infection.

The study objective factors were the presence or absence of intracameral cefuroxime and the use of intensive peri-operative levofloxacin versus intensive peri-operative placebo drops, which gave rise to a factorial design with four treatment groups. The peri-operative levofloxacin drops and placebo were masked. The intracameral cefuroxime was not masked, as the injection of a placebo alternative to cefuroxime was considered ethically questionable. The use or nonuse of intracameral cefuroxime was determined by a randomly generated number. The groups that received intracameral cefuroxime and the groups that received intensive levofloxacin were combined to permit a 2-x-2 factorial analysis.

An ASCRS criticism of the study is that only 50% of patients received a pre-op antibiotic drop just one hour before surgery while 100% of patients received post-op antibiotic drops commencing on day The patients randomly allocated to intensive peri-operative levofloxacin or placebo received these drops starting 60 minutes pre-op and concluding 30 minutes post-op. This peri-operative protocol was compared to intracameral cefuroxime. These intensive peri-operative drops were shown to have no statistical value in reducing the incidence of post-op endophthalmitis. The effect of the routine post-op levofloxacin drops q.i.d. for one week cannot be determined. It may have reduced the overall risk, but we will never know. Conversely, there was overwhelming evidence that the intracameral injection of cefuroxime 1 mg in 0.1 ml of normal saline reduced the incidence of post-op endophthalmitis by a factor of five. This five-fold reduction held true for both the total number of clinically presumed and clinically proven endophthalmitis cases. Endophthalmitis was deemed proven if the vitreous and/or anterior chamber tap yielded a positive culture, positive Gram stain, or positive polymerase chain reaction (PCR). Definitive conclusion We are therefore left with the inescapable conclusion that intracameral cefuroxime works. We can also deduce that the rate in the “minimal treatment” or “non-peri-operative antibiotic” group was high, 0.3%. This does not mean that Europe is a dirty place to have your cataract operation; rather, that reports in the literature understate the problem. Bad results can escape reporting and retrospective studies often underreport. Prophylactic povidone iodine alone may not be as effective as we thought.

While we are pleased with the study’s definitive outcome, we must now face the problems this outcome presents.

How is this implemented in practice?

If cefuroxime was a new drug that was sponsored and made available by a pharmaceutical company, the adoption of intracameral cefuroxime might be immediate and worldwide. However, cefuroxime is neither licensed nor commercially available for intraocular use. While a physician can take responsibility for using it off-licence but, this requires the dilution of the 750 mg of powdered cefuroxime to a dilution of 1 mg in 0.1 ml and exposes the user to the risks of “kitchen” pharmacy with potential errors of dilution, errors of diluent, possible induction of Toxic Anterior Segment Syndrome (TASS), and, frighteningly, possible contamination (e.g. by Pseudomonas), which is not sensitive to cefuroxime.

For this reason, we have appealed to the industry to provide us with a sterile single-unit dose of cefuroxime for intraocular use.

While we wait for this to happen, we advocate the widespread use of intracameral cefuroxime. Your hospital pharmacy can make up the antibiotic in a sterile environment with a shelf life of nine days, or you can do as most Swedish surgeons do and dilute it yourself in the operating room, despite the aforementioned risks. It is not ideal, but it is better than denial.

But, the question will always be asked,—“if cefuroxime is good, is vancoymycin, [off patent, Vanocin, Baxter Healthcare, Deerfield, Ill.], moxifloxacin, [Vigamox, Alcon, Fort Worth, Texas] or gatifloxacin, [Zymar, Allergan, Irvine, Calif.] or some other agent better?”

How to choose an effective agent

First, we must consider that vancomycin and the newer quinolones should be reserved for treatment and not used for prophylaxis.

Second, a demonstration of the superiority of intracameral moxifloxacin or gatifloxacin will take safety studies and a full fresh clinical trial, which may now be impossible to perform. Any trial excluding an intracameral antibiotic for any patient may be deemed unethical because of the ESCRS trial results, and any trial attempting to demonstrate the superiority of any intracameral agent to cefuroxime may be futile. Third, the comparative benefits of the newer quinolones applied topically compared to the intracameral cefuroxime used in our study will also require a large and expensive trial, which is superfluous if intracameral cefuroxime achieves the 0.05% rate that we have shown. The Swedish experience of seven years has shown the efficacy and safety of cefuroxime in more than 400,000 patients. The ESCRS study has proven it. If its use is adopted worldwide—pending studies showing other agents or delivery systems to be superior—then thousands of eyes will be saved from the potential ravages of post-op bacterial endophthalmitis following cataract surgery with IOL implantation, in which case, we urge you o employ it.

References:

1. Seal D, Barry P, Gettinby G, Lees F, Peterson M, Revie C, Wilhelmus K. ESCRS study of prophylaxis of post-operative endophthalmitis after cataract surgery: Case for a European multicentre study. J Cataract Refract Surg. 2006; 32: 396-406.

2. Barry P, Seal D, Gettinby G, Lees F, Peterson M, Revie C. ESCRS study of prophylaxis of post-operative endophthalmitis after cataract surgery: Preliminary report of principal results from a European multicentre study. J Cataract Refract Surg. 2006; 32: 407-410.

3. ESCRS Endophthalmitis Study Group. Prophylaxis of post-operative endophthalmitis following cataract surgery: results of the ESCRS multicentre study and identification of risk factors. J Cataract Refract Surg. In press.

Editors’ note: Dr. Barry and the ESCRS have no financial interests in any of the products used in this study.

ABOUT THE AUTHOR

Peter Barry, F.R.C.S. is consultant ophthalmic surgeon, Royal Eye and Ear Hospital and St. Vincent’s Hospital, Dublin, Ireland. He can be reached at peterbarryfrcs@eircom.net.

Perspectives in lens and IOL surgery The ESCRS endophthalmitis study— implications for now and the future Perspectives in lens and IOL surgery The ESCRS endophthalmitis study—
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