Endophthalmitis is the most serious complication of cataract surgery and can occur after routine cases. Although fortunately rare, this infection can blind patients, even after appropriate management. More than half of patients have less than 20/40 vision after bacterial endophthalmitis following cataract surgery, even with appropriate intervention.¹ The low incidence of endophthalmitis severely limits the opportunity for researchers to compare preventative measures in a scientific manner. We surgeons therefore have no large clinical trials to guide us in our choice of antibiotics for prophylaxis. We can consider the clinical experience of high-volume surgeons who report success with certain interventions, but this type of evidence does not have the same weight as a randomized clinical trial. Additionally, we must view retrospective clinical trials in the context of their design. For example, were the studies planned and powered to show differences among the interventions?

In the end, we often turn to surrogate measures of certain aspects of infection. We consider how antibiotics work to kill bacteria in a laboratory setting, how the drug penetrates the eye, or how an antibiotic performs in an animal model of infection.

This article discusses the value of sterilizing the ocular surface and the use of antibiotics around cataract surgery for the prevention of endophthalmitis.

STERILIZATION
Bacteria enter the eye during cataract surgery. If we could completely sterilize the ocular surface as well as the instruments and IOL entering the eye during surgery, this mode of infection would be eliminated.

Clearly, incisions can also allow bacteria to enter the eye during the first day or 2 after surgery, but the vast majority of incisions are probably secure as soon as they are covered by the epithelium. If endophthalmitis develops 1 or 2 weeks after surgery, when did the bacteria enter the eye? My suspicion is the bacteria entered the eye at the time of surgery or very soon after, because some bacteria can live in the eye for weeks or even months before producing the clinical signs of inflammation.²

The number of infections caused by bacterial infiltration during and after surgery is currently unknown and probably cannot be determined.

DRUG THERAPY
Today's topical corticosteroids are so potent that, in some cases, they may completely suppress the migration of white blood cells into the eye that is induced by organisms of low virulence. As the drops are tapered and the bacteria multiply, inflammation may arise well after the surgery. There is some evidence that topical antibiotics can treat endophthalmitis,^3,4 but we always rely on intraocular antibiotics when we suspect an infection is present. The use of topical antibiotics after cataract surgery may also suppress bacterial multiplication in the eye, but we would not want to rely on this mode of delivery to treat endophthalmitis.

In my view, topical antibiotics prevent endophthalmitis in two ways: (1) by reducing the number of organisms on the ocular surface and (2) by killing the bacteria that enter the anterior chamber during or after surgery. The critical period of therapy is just before surgery and until the wound no longer allows the ingress of organisms (probably 1 or 2 days after surgery in the vast majority of cases). A reduction in the amount of bacteria on the ocular surface at the time of surgery is best achieved through the application of a disinfectant. Povidone-iodine is routinely used and remains the most important intervention.⁵ The use of a topical antibiotic before surgery can further reduce the presence of organisms and can provide a depot of the antibiotic in the ocular tissues to suppress or kill organisms that enter the eye. After surgery, topical antibiotics continue to reduce the number of organisms on the ocular surface and kill those that enter the eye through an inadequately sealed wound. Based on this scenario, it makes sense to administer topical antibiotics for about 4 to 7 days after surgery. Longer therapy is probably of limited benefit.

WHICH ANTIBIOTIC DROP?
Cataract surgeons generally agree that fluoroquinolones provide the best combination of efficacy (good minimum inhibitory concentration and spectrum of coverage) plus superior penetration. The newer agents moxifloxacin and gatifloxacin offer better penetration than earlier formulations, with corneal and aqueous levels of moxifloxacin exceeding those of gatifloxacin.^6,7 Levofloxacin at the concentration of 1.5% should achieve higher concentrations in the human eye than the earlier formulation of this drug, but sufficient data are not available. It will be important to evaluate the penetration of the newest fluoroquinolone, besifloxacin. Rabbit models of endophthalmitis support the efficacy of both moxifloxacin and gatifloxacin drops in prevention of infection.^3,4

All of the most recently released fluoroquinolones have an excellent kill rate for bacteria on the ocular surface. The commercial preparation of gatifloxacin appears to eradicate bacteria more rapidly than moxifloxacin in some studies, a finding that may be attributable to the presence of benzalkonium chloride in the former drug.⁸

It is not clear if this advantage is clinically relevant when patients also receive multiple drops containing benzalkonium chloride (dilating and nonsteroidal drops) just prior to surgery. Other antibiotics such as aminoglycosides (tobramycin and gentamicin) and macrolides (erythromycin and azithromycin) have characteristics that make them less desirable for perioperative use.

In the absence of definitive studies, what should we do now? I recommend the use of a fluoroquinolone drop four times a day beginning 24 hours before surgery, resumed as soon after surgery as possible, and continued for 3 to 7 days. A reasonable case can be made for starting antibiotic drops 30 to 60 minutes before surgery rather than 24 hours. Clinical trials may refine our therapeutic strategies in the future. New developments in drug delivery will probably change our management strategies and may significantly reduce this rare but potentially devastating complication.

Michael B. Raizman, MD, is an associate professor of ophthalmology, Tufts University School of Medicine, the director of the Cornea and Cataract Service, New England Eye Center; and a partner at Ophthalmic Consultants of Boston. He is a consultant to Alcon Laboratories, Inc.; Allergan, Inc.; Bausch & Lomb; Inspire Pharmaceuticals, Inc.; and Vistakon. Dr. Raizman may be reached at (617) 367-4800-2656; mbraizman@eyeboston.com.

1. Josephberg RG. Endophthalmitis: the latest in current management. Retina. 2006;26:S47-S50.
2. Raizman MB. Management of postoperative complications: prolonged intraocular inflammation. In: Steinert RF, ed. Cataract Surgery: Technique, Complications & Management. Philadelphia, PA: WB Saunders Co.; 1995:439-442.
3. Kowalski RP, Romanowski EG, Mah FS, et al. Topical 0.5% moxifloxacin prevents endophthalmitis in an intravitreal injection rabbit model. J Ocul Pharmacol Ther. 2008;24(1):1-7.
4. de Castro LE, Sandoval HP, Bartholomew LR, et al. Prevention of Staphylococcus aureus endophthalmitis with topical gatifloxacin in a rabbit prophylaxis model. J Ocul Pharmacol Ther. 2006;22(2):132-138.
5. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with topical povidone-iodine. Ophthalmology. 1991;98(12):1769-1775.
6. Kim DH, Stark WJ, O'Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% ophthalmic solution in cataract surgery patients. Ophthalmology. 2005;112(11):1992-1996.
7. Holland EJ, Lane SS, Kim T, et al. Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty. Cornea. 2008;27(3):314-319.
8. Kowalski RP, Kowalski BR, Romanowski EG, et al. The in vitro impact of moxifloxacin and gatifloxacin concentration (0.5% vs 0.3%) and the addition of benzalkonium chloride on antibacterial efficacy. Am J Ophthalmol. 142(5):730-735.