Use of topical antibiotics with intravitreal injections: a controversy coming to an end
On 2 February 2018, Ophthalmologica published “2018 Update on Intravitreal Injections:
Euretina Expert Consensus Recommendations” (DOI: 10.1159/000486145) online, authored by Andrzej Grzybowski, Reinhard Told, Stefan Sacu, Francesco Bandello, Elad Moisseiev, Anat Loewenstein, and Ursula Schmidt-Erfurth on behalf of the Euretina Board.
The article was intended “to highlight important aspects of pre- and post-injection management by examining the recent literature for evidence-based suggestions providing a standardized and structured approach.”
On the long-debated issue of antibiotic prophylaxis, the authors concluded that, based on current evidence, “perioperative antibiotics cannot be considered the standard of care, as there is no evidence of prophylactic effects with regard to EO [endophthalmitis] when using perioperative antibiotics.”
In addition, large studies have reported a paradox effect, leading to increased rates of endophthalmitis due to repeated antibiotic exposure. Intravitreal injections are administered frequently and over the long term, and it should be kept in mind that “the widespread and frequent use of topical antibiotics promotes increasing resistance to antibiotic substances and growth of pan-drug-resistant bacteria,” the authors wrote.
Here are the opinions of experts from around the world on the topic.
Paolo Lanzetta, MD
Professor and Chair of the Department of Ophthalmology, University of Udine and Scientific Director of the European Institute of Ocular Microsurgery (IEMO), Udine, Italy
Jordi Monés, MD
Director of the Institut de la Màcula and Barcelona Macula Foundation, Barcelona, Spain
Frank Holz, MD
Professor and Chair of the Department of Ophthalmology, University of Bonn, Germany
Keith A. Warren, MD
Warren Retina Associates, Overland Park, Kansas, USA
Carl D. Regillo, MD, FACS
Director of the Retina Service, Wills Eye Hospital, Philadelphia, USA
There has been a strong trend away from the use of topical antibiotics with intravitreal injections. Only a very small minority still do it. We all used to do it, but it has fallen by the wayside for the most part and now it is pretty rare. Yes, nowadays to see the practice of using topical antibiotics after an intravitreal injection is very rare.
A lot of us used them at first, but as time went by studies seemed to indicate that it was not necessary. It didn’t really do anything above and beyond the standard Betadine prep.
Judy E. Kim, MD
Professor of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI, USA
I have not used topical antibiotics for intravitreal injection for some years now. Topical antibiotics before or after the injections have not shown to be beneficial in most cases. At Diabetic Retinopathy Clinical Research network (DRCR.net), we studied a large number of injections and were among the first to show that there was no benefit. There are also studies showing that repeated use of topical antibiotics can lead to growth of superbugs with drug resistance, which can actually be detrimental to the patients. In addition, use of antibiotics pose added cost and burden on the patients. Keeping the lashes away, not talking (or wearing a mask) during injections and the use of povidone iodine are some of the key steps in infection control related to intravitreal injections.
Pravin U. Dugel, MD
Retinal Consultants of Arizona, Phoenix, USA
We don’t use antibiotics we use Betadine. I use it in every patient that I inject. I don’t do an injection without Betadine preparation first. We don’t use antibiotics, but we always use Betadine.
Antibiotic prophylaxis is first of all very costly. Secondly, there are side effects in selecting out resistant organisms and there is very good evidence that with Betadine alone we do achieve a level of sterilization that is more than adequate.
I think the overwhelming majority of retina specialists in the US use Betadine alone.
J. Fernando Arevalo, MD, FACS
President of the Pan-American Association of Ophthalmology, Academia Ophthalmologica Internationalis Member (Chair: XXIX), Edmund F. and Virginia B. Ball Professor of Ophthalmology, Chairman, Department of Ophthalmology, Johns Hopkins Bayview Medical Center Retina Division, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Several studies have shown by now that in thousands of injections, the incidence of endophthalmitis without the use of antibiotics before or after injections is very low. In addition, the studies suggest that the use of prophylactic antibiotics may increase resistance and, in fact, increase the incidence of endophthalmitis. The reported endophthalmitis rates after IVT injection range from 0.020% to 0.085% (very low but they are zero as would be desirable). The two key issues involved in the prevention of endophthalmitis are pre-IVT injection disinfection using povidone-iodine (PVI) and the use of topical antibiotics as prophylaxis. Recent data suggest that there is inadequate evidence to support the routine use of prophylactic pre-, peri-, or postinjection antibiotics to reduce the risk of endophthalmitis. Pre-IVT injection disinfection using povidone-iodine (PVI) remains the gold standard. [Information cited comes from the following studies: Acute endophthalmitis after intravitreal injection and preventive effect of preoperative topical antibiotics.Park Y et al. J Ocul Pharmacol Ther. (2013). Prophylactic antibiotic use after intravitreal injection: effect on endophthalmitis rate.Bhatt SS et al. Retina. (2011). Intravitreal Injection–Technique and Safety.Lai TY et al. Asia Pac J Ophthalmol (Phila). (2015)]
Dhivya Ashok Kumar, MD
Dr. Agarwal’s Eye Hospital, Chennai, India
We do not combine intravitreal antibiotics for routine intravitreal injections like anti-VEGF or triamcinolone. However, we keep the patient on topical antibiotics, preferably fourth generation flouroquinolones, namely moxifloxacin qid after intravitreal injections, for 1 week. We take enough sterile precautions during intravitreal injections to prevent the transfer of microbes by treating periocular infections before taking the patient for injection. Pre-injection Betadine cleaning of the conjunctival sac and periocular tissue is mandatory in all our cases. All intravitreal injections are performed in a sterile operating room set up. Proper scrubbing, sterile precautions during injections, and regular checking of drug vial status reduce the risk of infection. Prophylactic antibiotics orally are also given for 5 days following intravitreal injections. Immediate instillation of topical antibiotics by the end of the intravitreal procedure and good postoperative follow-up is required. Many of our eye care centers in this part of the country follow the same protocol. Intravitreal antibiotics are given only in cases with endophthalmitis or suspected endophthalmitis.
Sundaram Natarajan, MD
Professor and Chairman, Aditya Jyot Eye Hospital, Mumbai, India
In India, many of us use antibiotic drops, the day before and in the three days post-injection. On the day of the injection, we use povidone iodine, and we perform the injection in the operating room.
The Vitreo-Retina Society of India still recommends this practice. We have discussed changes in many of the current practices, but there has been no discussion yet on the use of antibiotics. Personally, I think that we should align with other countries and release recommendations that povidone iodine alone is sufficient to prevent infection.
We have had clusters of endophthalmitis with Avastin, likely due to contamination during preparation of the drug, but with the other drugs, Lucentis and Eylea, endophthalmitis is extremely rare.
Tien Y. Wong, MD, PhD
Professor and Chairman, Department of Ophthalmology, National University of Singapore, Singapore
There is clearly no evidence in the literature and the guidelines on injections do not support routine use of topical antibiotics. I perform intravitreal injections in a clean room in the office setting. Clean with iodine, drape and speculum. No antibiotics are used. We are now progressing to nurse-led injection clinics for simple cases.
Anat Loewenstein, MD, MHA
Professor of Ophthalmology and Deputy Dean, Medical School, Sackler Faculty of Medicine, Tel Aviv University, and Chairman of the Department of Ophthalmology, Tel Aviv Sourasky Medical Center (TASMC, Tel Aviv, Israel )
I do not prescribe topical antibiotics prior to the administration of intravitreal injections. There have been no prospective studies demonstrating that pre-injection antibiotics reduce the risk of endophthalmitis. Moreover, the repetitive nature of intraocular injection of anti-VEGF agents, and thus repeated use of topical antibiotics, dramatically increases the potential for colonization of the ocular surface with resistant bacteria. Also, the use of antibiotics prior to intravitreal injection increases cost and patient inconvenience, particularly when patients are managed in an [as-needed] PRN manner.
We still give one drop of antibiotic at the end of the procedure, as this is the common practice in my country. Nevertheless, it should be noted that topical antibiotic use at the time of the injection procedure offers no additional benefit over topical broad-spectrum microbicides and antiseptic administration.
Topical antibiotic use after the injection procedure also offers no reduction of endophthalmitis risk. In fact, topical antibiotics have poor penetration into the eye due to various physiological barriers, so they do not reach therapeutic levels in the vitreous.
Antibiotic resistance is a serious concern. In multiple large case series comparing intravitreal injection with or without the use of antibiotics, there is a numerical trend in most cases toward increased rates of endophthalmitis when antibiotics are used.