Current thinking on prophylaxis of an infection after cataract surgery has been shaped by information from numerous sources. Factors include the source of the infecting organisms, how infecting organisms gain access to intraocular spaces, the incidence of infection, pathogens and their patterns of resistance, the pharmacokinetics and spectrum of activity of antimicrobials and antiseptics, the ocular penetration of antimicrobials, and the variables of the wound's construction and integrity.

As ophthalmologists, we know that the patient's own periocular flora is the source of an infection in most cases¹ and that large-scale clinical trials have shown that povidone-iodine preparation of the eyelids and conjunctiva is effective at reducing the incidence of endophthalmitis.² This information has inspired considerable efforts to improve prophylaxis. In a study of the use of 5% povidone-iodine, an irrigation of 10 mL was found to be more effective in reducing bacterial colonization than two drops instilled in the conjunctival sac.³ Another important piece in the prophylactic puzzle came from a 2006 ESCRS study of 16,000 patients. In it, intracameral cefuroxime reduced the risk of postoperative endophthalmitis fivefold,⁴ lending further credibility to the efficacy of antimicrobial prophylaxis.

This article focuses on current prophylactic approaches and the available agents.

PROPHYLACTIC SAFETY
There have long been concerns about the intracameral administration of antibiotics for routine prophylaxis because of uncertainties about toxicity and the accuracy of dosing. The adoption of intracameral cefuroxime, for example, was limited by the lack of a commercially available preparation to avoid dosing errors, deficiencies in the pharmacokinetics and spectrum of activity, and the potential for anaphylaxis. There is currently significant interest in evaluating moxifloxacin for intracameral prophylaxis because of its commercial availability in a preservative-free preparation and its superior spectrum and kinetics. During this evaluative process, we should continue to emphasize preoperative prophylaxis with topical agents.

The varied practices of cataract surgeons, with regard to topical prophylaxis, reflect the lack of definitive information about the efficacy of current strategies to prevent endophthalmitis. The goals of prophylactic antimicrobial therapy are to achieve levels in the target tissues well in excess of the minimum inhibitory concentrations (MICs) for the commonly responsible pathogens and to maintain these levels for a period of time sufficient to kill the organisms without causing toxicity to ocular tissues. The safety of preoperative topical prophylaxis compared with the potential risks of intracameral administration is important. Topical fourth-generation fluoroquinolones have characteristics that make them desirable for prophylaxis. They are effective against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, several species of streptococcus, enterococcus, and bacillus. These drugs demonstrate greater potency compared with third-generation fluoroquinolones such as ofloxacin, ciprofloxacin, and levofloxacin. Topical fourth-generation fluoroquinolones kill bacteria rapidly, and the acquisition of resistance requires a two-step mutation.

Moxifloxacin has unique solubility properties in lipids and water that allow it to rapidly penetrate the cornea. Ocular penetration studies have shown that the fourth-generation agents moxifloxacin 0.5% and gatifloxicin 0.3% are able to achieve higher levels in the aqueous after topical administration than third-generation agents such as ciprofloxacin.⁵ In addition, moxifloxacin 0.5% has the advantage of being supplied at a higher concentration than gatifloxacin 0.3%. After topical administration in numerous studies,^6-8 moxifloxacin achieved aqueous concentrations twofold higher than did gatifloxacin. Relative to the antibiotic sensitivity of the most common bacterial pathogens, the aqueous levels achieved after four topical doses given immediately preoperatively were more likely to reach bactericidal levels with moxifloxacin than gatifloxacin^6,7 (Figure 1). A comprehensive review of the clinical and laboratory evidence for the superiority of moxifloxacin over gatifloxacin for prophylaxis was recently published.⁸

WHEN TO START TOPICAL ANTIBIOTIC THERAPY
The best time to start topical antibiotic therapy prior to cataract surgery is still in question. In the absence of studies that look at the rate of infection as a function of a preoperative dosing schedule, we have to consider the effect of dosing schedules on either the achieved aqueous levels of an antibiotic or the effect on numbers of bacteria recovered by cultures from the conjunctiva. The currently available data suggest that moxifloxacin, when administered every 10 minutes for a total of four doses immediately prior to surgery, achieves aqueous levels that are similar to those produced by dosing for 1 to 3 days prior to surgery.^6-8 Other studies that have looked at the recovery of bacteria by culture, however, show an advantage of 1 to 3 days of q.i.d. dosing over shorter periods.^9,10 The potential for toxicity and noncompliance increases with longer dosing schedules, and complete sterilization of the external eye with any regimen is unlikely. Because the aqueous levels achieved with several doses of moxifloxacin in the immediate preoperative period are well in excess of the MICs of the important pathogens, and because the effect is additive to that of povidone-iodine,¹¹ a convincing argument can be made that longer preoperative treatment with moxifloxacin is unnecessary.

Combining oral and topical ofloxacin increases the penetration of the drug into the vitreous.¹² Oral administration of 400 mg of moxifloxacin achieves levels in the vitreous above the MICs thought to be effective, and the aqueous levels achieved by dosing over several days appeared to be greater than immediate preoperative dosing alone.¹³ In cases that are at higher risk for infection such as when there is an open capsule with communication between the anterior chamber and the vitreous cavity,¹⁴ the use of oral moxifloxacin may be considered.

CONCLUSION
Existing information is inadequate to determine the optimally effective prophylactic regimen. Currently available data, however, support the following strategies for preventing infection after cataract surgery: preoperative prophylaxis with topical moxifloxacin, povidone-iodine preparation of the lids and conjunctiva, draping of the lids and lashes, a watertight wound at the end of the procedure, and the postoperative use of moxifloxacin for several days.

Mark Speaker, MD, PhD, is an attending surgeon, Cornea Service, The New York Eye and Ear Infirmary; an associate clinical professor of ophthalmology at the New York Medical College; and the medical director of TLC Laser Eye Centers in New York. Dr. Speaker may be reached at (212) 832-2020; mspeakermd@gmail.com.

Neeti Parikh, MD, is a fellow for cornea and refractive surgery at The New York Eye and Ear Infirmary. Dr. Parikh may be reached at (212) 832-2020; np619@hotmail.com.

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