Intracameral antibiotic prophylaxis gains wide acceptance, but questions remain

Seven years after publication of the European Society of Cataract and Refractive Surgeons endophthalmitis study results, intracameral antibiotic prophylaxis has gained wide acceptance in many countries as the most effective way to prevent postoperative endophthalmitis in cataract surgery. A fivefold reduction in the incidence of this complication was shown at the time, and since then, other large studies have been performed, leading to comparable results.

As reported in the recent ESCRS Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery, “a striking drop from rates near 0.3% – 1.2% prior to the institution of intracameral cefuroxime, to rates of only 0.014% – 0.08% after institution of intracameral cefuroxime” was shown in areas of France, Spain and South Africa, as well as by the Swedish cataract registry, which now has 500,000 cases. A study in Singapore, conducted on 50,000 patients, showed a decrease from the previous already low rate of 0.06% to 0.01% with intracameral cefazolin.

“A 7- to 28-fold reduction, wherever this decision [to use intracameral antibiotics] has been taken,” Peter Barry, FRCS, FRCOphth, FRCSI, ESCRS study chairman, said.

In Israel, a survey on practice patterns and surgical complications performed annually among all ophthalmology surgical centers showed that the endophthalmitis rate was as high as 0.16% in 2003, Ehud I. Assia, MD, OSN Europe Edition Board Member, said. Thereafter, a gradual decrease of 0.01% to 0.02% per year was documented, reaching an incidence of 0.09% in 2007 and 0.03% in 2013.

“There is a good correlation between the increased use of intracameral antibiotic injection and the decreasing rate of endophthalmitis,” he said.

Most cataract surgeons in his country follow ESCRS recommendations and would consider it unethical or even illegal to do otherwise.

Ophthalmologists in North America are still reluctant to follow the recommendations, primarily due to concerns regarding the off-label use and extemporaneous compounding of cefuroxime. Swimming against the tide, a group in California, U.S.A., decided to adopt intracameral prophylaxis, progressively broadening the indications to all patients. The endophthalmitis rate decreased from the initial 0.31% to 0.014%.

“A rather overwhelming evidence,” Barry said. “Hopefully, this study represents the chink in the armor that will help open the door to intracameral prophylaxis in the U.S.”

Single-dose preparation of cefuroxime

An ESCRS survey carried out in 31 countries in Europe reported an overall utilization rate of 74%, with a steady increase. In addition, the European Medicines Agency recently approved Aprokam (Laboratoires Théa), a single-dose preparation of cefuroxime specifically designed for intracameral administration. Currently available in 17 countries, it should be introduced in at least five more this year.

Price variations, as well as various regulatory processes and reimbursement policies, account for different penetration rates of Aprokam across countries.

“The problem with Aprokam is that it turns out to be 20-fold more expensive than extemporaneous cefuroxime compounding,” Oliver Findl, MD, said.

He estimated that intracameral antibiotic prophylaxis is now used by approximately 80% of the surgeons in Austria, but the individual doses are mostly prepared by hospital pharmacies.

“Contamination is not my concern, since our pharmacies work under stringent sterile compounding rules,” he said.

In other countries, Aprokam has turned out to be more convenient than a compounding pharmacy.

“The cost in Ireland is €110 for a box of 10, which accounts for €11 per patient. In our university hospital, we have chemotherapeutic facilities, and cefuroxime is prepared in single doses once a week for all cataract patients under absolute sterile conditions. However, other hospitals find it is easier, safer and even cheaper to use Aprokam,” Barry said.

In Italy, variations exist within regions. Although approved by the ministry of health, Aprokam has not yet been included in the drug formulary by the local health authorities of some of the regions.

“We’ll be happy to use it when it becomes available. Until then, I will continue using the Gimbel method of adding antibiotics in the irrigating solution. I do about 5,000 cataract operations per year, and this prophylaxis has maintained my endophthalmitis rate down to practically zero for many years. I prefer to go my old way rather than use an off-label procedure,” Alessandro Galan, MD, OSN Europe Edition Board Member, said.

Similar concerns seem to be shared by a fair number of Italian ophthalmologists. A survey carried out by the Italian Association of Cataract and Refractive Surgery showed that less than 50% of surgeons have followed the ESCRS recommendations over the past 6 years, while 75% of surgeons use topical antibiotics preoperatively and 100% use them postoperatively.

“I believe that Aprokam will change our habits quite dramatically,” Galan said.

Use of topical antibiotics

The use of topical antibiotics in addition to intracameral prophylaxis is a current controversy. Several reports quoted by the recently released ESCRS guidelines led to the conclusion that no clear benefit has been established. In addition, concerns have been raised by the steadily growing bacterial resistance to antibiotic agents, including fluoroquinolones.

“We do not use antibiotics preoperatively. Postoperative antibiotics, most commonly third- and fourth-generation fluoroquinolones, are often given for 1 week,” Assia said.

According to Findl, no additional antibiotics are required unless the patient presents with specific conditions. All that is needed in addition to intracameral prophylaxis is a strict antisepsis protocol, giving povidone-iodine a sufficient time of at least 5 minutes to be effective against infectious agents, he said.

Adherence to OR hygiene protocols is critical but not always fully complied with, Galan said.

“The casual negligence, like an anesthesiologist who doesn’t wear a cap or a nurse who goes in and out with the same pair of clogs and even a surgeon who doesn’t wear a face mask, is often seen in real life and might lead to dramatic consequences. The sanitation of the room and instruments after each procedure is mandatory. An operating microscope that is not properly disinfected can be the source of many contaminating organisms,” he said.

Galan still uses topical drops before and after the procedure and believes that if broad-spectrum antibiotics are used, there should be no problems with resistant bacteria.

He also said that the best prevention is meticulous, fast and minimally traumatic surgery.

“I believe that the higher rate of endophthalmitis in the past can be at least partly explained by the longer, debilitating, less accurate surgery we used to perform,” he said.

Intravitreal injections

Prevention of endophthalmitis with intravitreal injections is a new challenge, and no uniform agreement exists among vitreoretinal surgeons, Barry said.

“There is very little data, an awful lot of confusion, no guidelines and huge variability in the way prevention is done,” he said.

There are concerns that routine use of topical antibiotics after intravitreal injection might create an environment for the development of resistant bacteria, ready to invade the eye when the next injection is scheduled 1 month later.

“Cataract happens twice, once right and once left. But patients who receive intravitreal injections might receive 40 or more over a few years, and this definitely poses a hazard,” Findl said.

In his department, about 4,000 injections are performed per year in the OR with a strict disinfection and sterilization protocol. No antibiotics are used, but the infection rate is near zero.

According to Galan, who has 1,700 injections performed yearly in his department, antibiotic drops should be used in addition to stringent rules in the OR. He said they should not cause any problems, provided that the injections are performed at least 1 month apart.

Consensus on a protocol for asepsis and antisepsis and an acceptable prophylactic regimen are necessary, Barry said.

“We are talking about an elderly, frail population, where numbers are now overwhelming and on the increase,” he said.

 The joint forces of ESCRS and Euretina are currently planning a registry of cases. Based on the information collected, a study and a plan for the future will be designed. – by Michela Cimberle

• References:
• Barreau G, et al. J Cataract Refract Surg. 2012;doi:10.1016/j.jcrs.2012.03.024.
• Barry P, et al. ESCRS guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusion. www.escrs.org/downloads/Endophthalmitis-Guidelines.pdf. Published 2013.
• Barry P. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2013.11.002.
• ESCRS Endophthalmitis Study Group. J Cataract Refract Surg. 2007;doi:10.1016/j.jcrs.2007.02.032.
• Friling E, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.10.037.
• García-Sáenz MC, et al. J Cataract Refract Surg. 2010;doi:10.1016/j.jcrs.2009.08.023.
• Montan PG, et al. J Cataract Refract Surg. 2002;28(6):977-981.
• Rodríguez-Caravaca G, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2013.03.031.
• Shorstein NH, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.07.031.
• Tan CS, et al. J Cataract Refract Surg. 2012;doi:10.1016/j.jcrs.2011.09.040.
• van der Merwe J, et al. J Cataract Refract Surg. 2012;doi:10.1016/j.jcrs.2012.09.004.
• For more information:
• Ehud I. Assia, MD, can be reached at Ein Tal Eye Center, 17 Brandeis St., Tel Aviv 62001, Israel; +972-3-543-3222; fax: +972-3-544-1222; email: assia@netvision.net.il.
• Peter Barry, FRCS, FRCOphth, FRCSI, can be reached at Royal Victoria Eye & Ear Hospital, Adelaide Road, Dublin 2, Ireland; +353-128-37203; fax: +353-128-38229; email: peterbarryfrcs@eircom.net.
• Oliver Findl, MD, can be reached at Department of Ophthalmology, Hanusch Hospital, Vienna, Austria; email: oliver@findl.at.
• Alessandro Galan, MD, can be reached at Ospedale Sant’Antonio, Centro San Paolo, Via Facciolati 71, Padova, Italy; +39-049-8216780; fax: +39-049-8216541; email: alessandro.galan@gmail.com.

Disclosures: Assia, Barry, Findl and Galan have no relevant financial disclosures.

Given the minimal trauma induced by modern vitrectomy procedures, should EVS indications for immediate vitrectomy be broadened to a larger number of cases?

Tap and inject still only proven standard of care for patients with hand motions or better presenting vision

The Endophthalmitis Vitrectomy Study (EVS), a multicenter randomized trial comparing vitrectomy to tap with injection of intravitreal antibiotics, demonstrated that vitrectomy was clearly beneficial for patients with post-cataract extraction endophthalmitis who presented with light perception vision and possibly for diabetic patients regardless of presenting vision. However, just as important, this clinical trial showed that vitrectomy did not provide any benefit in terms of vision gain over vitreous tap and injection for patients who presented with hand motions or better vision. Approximately two-thirds of these patients achieved 20/40 vision and about 85% achieved 20/100 vision regardless of whether they had more invasive vitrectomy or the less invasive tap with injection of antibiotics.

The goal of vitrectomy is to decrease the vitreous bacterial load, remove toxins and possibly allow for better intravitreal diffusion of antimicrobials. Even if simpler vitrectomy approaches can be employed, the surgical goals would be the same. Simpler approaches do not alter the fact that vitrectomy does not provide an advantage in visual outcome for this group of patients over tap and inject.

 In fact, there are multiple advantages to the less aggressive tap-and-inject approach because it does not require using an operating room and can be done right in the office. It is less expensive for the patient or carrier and more convenient for both the patient and physician. Also, treatment can typically be administered much more quickly in the office than having to wait to get into an operating room, a possible advantage in a rapidly progressive disease.

Our treatment decisions should be evidence based. Even if vitrectomy surgery is “easier” now than it was in the mid-1990s, in the absence of data showing it is a better procedure than tap and inject for the subset of patients who present with hand motions vision, there is no reason to choose a more invasive and more expensive procedure when a simpler, less invasive one works just as well.

Bernard H. Doft, MD, is a clinical professor of ophthalmology at the University of Pittsburgh School of Medicine and a founding partner of Retina Vitreous Consultants, Pittsburgh, U.S.A. Disclosure: Doft has no relevant financial disclosures.

Early vitrectomy improves outcomes

Although the EVS was a milestone in our understanding of endophthalmitis and endophthalmitis management, the recommendations that emerged at the time no longer conform to our current knowledge and emerging developments. In fact, it is my opinion that the EVS should be repeated now for more updated results.

The perspectives we have today in the treatment of endophthalmitis are totally different from what they used to be nearly 20 years ago. First of all, vitrectomy is not as aggressive as it was before. Second, we know more about the cascade of events that leads to progressive and rapid ocular damage even in the early stages. Early surgery is the only effective weapon we have to improve the outcomes of endophthalmitis management. On the other hand, evidence shows that the efficacy of intravitreal cortical steroids is more and the toxicity of antibiotics is less in the early stages than later, when the retina is heavily inflamed.

Whenever I see the clinical signs of endophthalmitis, I perform a vitreous tap under the operating microscope, and if there is evidence that the vitreous is affected, I perform 25-gauge complete vitrectomy immediately. This is to prevent the infection from reaching the retina. Postponing would only expose the patient to unnecessary complications. Intravitreal antibiotics are also injected at the end of the procedure, and any inflammatory debris should be removed to minimize the toxicity of inflammatory products and infectious agents present in the vitreous cavity, leaving the eye as clean as possible.

Jorge L. Alió, MD, PhD, is an OSN Europe Edition Board Member and medical director at Vissum Corporation, Alicante, Spain. Disclosure: Alió has no relevant financial disclosures.