Eliminating infection: beyond a sterile surgical field

Research targets infective agents in an effort to arm surgeons in the war against endophthalmitis

TARPON SPRINGS, U.S.A. — Endophthalmitis remains an exceedingly infrequent complication of cataract and refractive surgery. Its potentially devastating results, however, push researchers increasingly harder to identify new interventions to help improve the present rate of poor visual outcomes associated with this infection. Meanwhile, cataract and refractive surgeons aim to fend off infection by maintaining as sterile a surgical field as possible and by continuing to use antibiotic prophylaxis even in the face of criticism from the research community regarding growing antibiotic resistance.

The surgeons’ perspective

University of South Florida Clinical Professor of Ophthalmology James P. Gills, MD, was a long-time proponent of infusing antibiotics into the eye throughout cataract surgery by means of the irrigating solution. Dr. Gills has made the switch to delivering antibiotics by means of intraocular injection at the end of the case for several reasons. “I put all of my antibiotics and steroids and non-steroidals in the eye at the end of the procedure, so I get a consistent dosage,” Dr. Gills said. “When we put it in the eye at the end of the procedure, we are trying to ensure that it’s a sterile container, and none of the bacteria that are inside the eye are going to get out and develop a resistance. So theoretically the eye is a contained area, and therefore whatever happens inside it isn’t going to develop resistant organisms in the community. It may develop [resistant organisms within the eye itself], but it’s a lot better to develop a resistant organism than to lose a bunch of eyes because of infection.”

Roger F. Steinert, MD, of Ophthalmic Consultants in Boston, pointed out that although attempting to maintain a sterile surgical field is one of the ways physicians try to minimize the introduction of infectious organisms into the eye, “a number of studies have proven that it is impossible to obtain a truly sterile surgical field in essentially any kind of surgery, so in ophthalmology we certainly do not have a totally sterile field no matter what we do. This is a very difficult field to study because the rate of endophthalmitis is so low that even in the past when no antibiotic prophylaxis was given [at cataract surgery] and essentially nothing was done other than very ordinary prepping and draping, the rate of endophthalmitis was typically under 1 in 1,000.”

With regard to refractive surgery, Dr. Steinert said there has been a bit more attention to infection-prevention with regard to laser in situ keratomileusis (LASIK) than with photorefractive keratectomy (PRK). “Although the surface is violated in PRK and there’s a potential for infection until that surface defect heals, at least it’s on the surface. With LASIK, there’s a smaller defect and it heals more quickly, but if any organisms get into the interface, they have the opportunity to multiply and divide in a relatively protected environment. I think that the general feeling is that the overall infection rate is a little lower in LASIK than in PRK, but that if you do get an infection with LASIK, it’s potentially much worse.”

The research perspective

Endophthalmitis is the most common blinding complication of cataract surgery. It is a particularly devastating infection for several reasons, according to a report from the Molecular Pathogenesis of Eye Infections Research (MPEIR) Center. First, unlike infections at other body sites, the interior of the eye is lined with neural tissues that do not regenerate once they are damaged. Loss of vision resulting from infection within the eye is, therefore, often permanent. Secondly, the interior chambers of the eye are physically separated from direct contact with the bloodstream by means of blood-ocular barriers. Normal defense mechanisms, therefore, are not readily available to halt infection in its early stages, and microbes freely multiply within the eye unchecked. Lastly, blood-ocular barriers are eventually breached by the immune system in an attempt to clear the infection. However, the intense inflammatory reaction that often develops within the eye may itself have serious consequences, with sensitive neural tissues being damaged by the toxic byproducts of inflammatory cells and serum factors. Treatment of endophthalmitis must therefore be directed not only at eliminating the infectious agent, but also at limiting blinding complications from the inflammatory response, as well. The MPEIR was established at the Dean McGee Eye Institute in the Department of Ophthalmology at the University of Oklahoma Health Sciences Center in Oklahoma City in 1994 to provide an interdisciplinary environment for research into debilitating infectious diseases of the eye.

Staphylococcus aureus is a leading cause of endophthalmitis and is associated with a bad visual outcome approximately 50% of the time. The recent trend toward increased antibiotic resistance among staphylococcal strains threatens to worsen the rate of treatment failure for this organism. MPEIR scientist Mary Booth, PhD, is researching the factors affecting the severity of endophthalmitis under a National Eye Institute grant. Dr. Booth is an assistant professor in the Department of Ophthalmology at Dean McGee Eye Institute. She aims to characterize S aureus endophthalmitis with respect to the role of toxins and other cellular factors that may contribute to severity. Examples of toxins implicated in these infections are toxic shock syndrome toxin-1 (TSST-1), exfoliative toxins A and B, and the superantigen entertoxins (SEA, SEB, SEC1, SEC2, SEC3, SED and SEE), respectively. One or a number of the extracellular toxins expressed by S aureus may contribute to the severity of endophthalmitis. By identifying such factors, new targets for therapeutic intervention may be revealed to augment current therapeutic strategies and significantly improve the present rate of poor visual outcomes associated with endophthalmitis.

According to MPEIR scientist Brad Jett, PhD, both the relative severity of endophthalmitis and the prognosis for favorable outcomes are largely dependent upon the pathogenic potential of the infecting organism and the host inflammatory response within the eye. Dr. Jett is assistant professor, Department of Biology, Oklahoma Baptist University. He has demonstrated that a bacterial toxin was responsible for destruction of ocular tissues during endophthalmitis using mutant organisms defective in toxin production. It is a central goal of Dr. Jett’s laboratory to characterize in detail the interaction between organism and host during intraocular infection. According to an MPEIR report, an understanding of these events may reveal specific targets to which therapeutic agents could be directed. n

For Your Information:

James P. Gills, MD, can be reached at St. Luke’s Cataract and Laser Institute, 43309 U.S. Highway 19 N, P.O. Box 5000, Tarpon Springs, FL 34688-5000 U.S.A.; +(001) 727-938-2020; fax: +(001) 727-938-5606; e-mail: jgills@jpgprops.com. Dr. Gills has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Roger F. Steinert, MD, can be reached at Ophthalmic Consultants, 50 Staniford St., Sixth Floor, Boston, MA 02114 U.S.A.; +(001) 617-367-4800; fax: +(001) 617-589-0714. Dr. Steinert has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Mary C. Booth, PhD, can be reached at Department of Ophthalmology, Room 403, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104-5065 U.S.A.; +(001) 405-271-1084; fax: +(001) 405-271-3013; e-mail: mary-booth@ouhsc.edu. Dr. Booth has no direct financial interest in any of the products mentioned in this article, nor is she a paid consultant for any companies mentioned.

Brad Jett, PhD, can be reached at Department of Biology, Oklahoma Baptist University, 500 W. University, Shawnee, OK 74804; fax: +(001) 405-878-2050; e-mail: Brad_Jett@mail.okbu.edu. Dr. Jett has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.