Intravitreal injections have rapidly become one of the most common medical procedures in the United States, with 1 270 836 intravitreal injections performed for Part B Medicare recipients in 2009 (Ross Brechner, personal communication, 2011). Associated endophthalmitis is a rare complication with potentially devastating consequences and a well-documented incidence, occurring after approximately 1 out of 1000 to 5000 injections.
Toward the goal of endophthalmitis prevention, certain methods in patient preparation have become common practice and guidelines have been published. Most recently, streptococcal species have been reported to cause a significant proportion of postinjection endophthalmitis (15%–42%), suggesting the possibility of injection site contamination by aerosolized nasopharyngeal moisture droplets, leading authors to recommend wearing surgical masks or minimizing talking while preparing and administering intravitreal injections. While many of these recommendations have not been evaluated in prospective randomized trials, much can be gleaned from analysis of existing literature. Two major points of interest are the use of antisepsis and antibiotics.
Antisepsis
Povidone-iodine (PI) provides broad-spectrum microbicidal activity when used for perioperative ophthalmic antisepsis. The povidone component is hydrophilic and acts as a carrier to transfer bactericidal iodine to the prokaryotic cell membrane, causing rapid cytotoxicity. Specifically, the kill time for PI is short, ranging from 15 to 120 seconds for concentrations of 0.1% to 10%, and PI has been shown to be bactericidal over a wide range of concentrations (0.005% to 10%). PI is inexpensive, with the average cost of a 30-mL bottle of 5% ophthalmic preparation solution being $12.00 ( www.redbook.com ).
Topical PI before cataract surgery has been shown to significantly decrease the rate of postoperative endophthalmitis in a prospective trial, and there are no reported cases of resistance to its bactericidal effects. More recent data suggest regular application of PI during cataract surgery may provide benefit in addition to application before surgery.
Adverse reactions to PI are usually related to its irritant effect or an allergic contact dermatitis. Anaphylaxis to iodine does not exist and there have been no reported cases of anaphylaxis to PI related to ophthalmic use. Following the routine use of PI when preparing the eye for an intravitreal injection, many clinicians apply additional PI to the conjunctiva immediately preceding insertion of the needle through the pars plana. If a small amount of PI is inadvertently introduced into the vitreous cavity during the injection, it is unlikely to cause a problem; animal models have shown ocular tolerance following intravitreal injection of significant volumes of PI.
Chlorhexidine has been reported to be more effective than PI at reducing surgical site infections in some instances, such as during central line placement and general surgery preparation. However, chlorhexidine can be toxic to the corneal endothelium and is potentially ototoxic. In most situations, chlorhexidine should not be used to prepare the eyelids and ocular surface before intraocular surgery.
Antibiotics
Prophylactic topical antibiotics are frequently used in patients undergoing intravitreal injections. Topical antibiotics before the day of injection do not reduce the rate of postinjection endophthalmitis and do not reduce conjunctival bacterial counts more than immediate preinjection PI application. A recent prospective study found that topical moxifloxacin 0.5% had no additional effect on reducing conjunctival bacterial counts beyond the effect of 5% PI alone. In the event that endophthalmitis does develop, preinjection antibiotics may increase the risk of resistance of the causative organism. Topical antibiotics have significantly longer kill times than PI, so when antibiotics are given immediately prior to an intravitreal injection, there is insufficient time for an adequate biological effect. Therefore, preinjection antibiotics either before the day of injection or immediately prior to injection are not generally recommended.
Application of topical antibiotics following intravitreal injection is also a common approach. Fluoroquinolones are frequently used because of their benign side-effect profile and because of their broad spectrum of antimicrobial activity. Although the goal of using these antibiotics is to reduce ocular surface flora, the true value of this prophylaxis is debatable and recent data suggest that we should reconsider this practice. First, topically applied fluoroquinolone antibiotics do not attain sufficient therapeutic levels in the vitreous cavity. Furthermore, analysis of antibiotic susceptibility patterns among conjunctival isolates from patients undergoing intravitreal injections found most organisms sensitive to gentamicin (≥85%) and fewer isolates sensitive to fluoroquinolones, with resistance rates to ciprofloxacin, levofloxacin, and gatifloxacin being 42%, 39%, and 22% respectively. Others have reported a high rate of fluoroquinolone resistance among bacterial isolates recovered from patients with endophthalmitis, and recent application of topical fluoroquinolones has been associated with fluoroquinolone resistance. Such resistance appears to be increasing and it is of interest that all cases of culture-positive endophthalmitis reported in a recent retrospective study were prescribed postinjection topical fluoroquinolones. Most concerning is the finding that exposure of ocular and nasopharyngeal flora to topical ophthalmic antibiotics led to the emergence of resistant strains. This problem may be especially true in the setting of monthly intravitreal injections in which the same topical antibiotic is used repeatedly in the same eye.
The average wholesale cost of commonly prescribed topical antibiotics given for post–intravitreal injection prophylaxis is between $8 and $90 ( www.redbook.com ). Such medications include polymyxin B/trimethoprim, gentamicin, gatifloxacin, and moxifloxacin. Therefore, if we assume all patients were given post–intravitreal injection antibiotics, in 2009 the cost to the United States health care system attributable to these prescriptions to Part B Medicare recipients alone was between approximately $10 000 000 and $114 000 000.
The Ophthalmic Mutual Insurance Company (OMIC) provides malpractice insurance for approximately 25% of ophthalmologists in active practice in the United States. From 2006 through the first quarter of 2011, OMIC has received no claims or lawsuits related to intravitreal injection endophthalmitis prophylaxis or lack thereof. Therefore OMIC states, “Decisions regarding use of antimicrobial and antiseptic prophylaxis should be based on best available science and not risk mitigation” (David W. Parke, II, MD, Chair, Claims Committee, OMIC, personal communication, 2011). In light of these factors, many practitioners are trending away from routinely dispensing postinjection antibiotics and large clinical trials suggest they may not be necessary.
Antisepsis has proven efficacy and plays an important role in ocular preparation for intraocular procedures, whether before cataract surgery or before intravitreal injection. PI has the advantages of low cost, broad-spectrum activity, widespread availability, fast bactericidal rate, and absence of resistance. In comparison, available data increasingly indicate that topical antibiotics either before or after intravitreal injection are not necessary, provide a large monetary burden to our health care system, and may be counterproductive by contributing to bacterial resistance. The community standard continues to evolve, but there appears to be a shift towards focusing on antisepsis and away from the use of peri-intravitreal injection antibiotics.
Publication of this article was supported by the National Institutes of Health center (Bethesda, Maryland) grant P30-EY014801 , and an unrestricted grant to the University of Miami from Research to Prevent Blindness (New York, New York). Funding sources had no role in design or conduct of this research. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Flynn has served as a consultant for Alcon, Allergan, Eli Lilly, Pfizer, and Santen. Dr Wykoff has served as a consultant for Eyetech. Involved in design of study (C.C.W., H.W.F., P.J.R.); conduct of study (C.C.W., H.W.F., P.J.R.); collection of data (C.C.W., H.W.F., P.J.R.); management, analysis, and interpretation of data (C.C.W., H.W.F., P.J.R.); and preparation, review, and approval of the manuscript (C.C.W., H.W.F., P.J.R.).
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