Diffuse lamellar keratitis, endotoxin, and ophthalmic sponges

Abstract

In response to a recent editorial on diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK),1 we would like to continue the discussion on bacterial endotoxin. Several studies using animal models have shown that endotoxin can cause DLK.2–4 Endotoxin may be the primary cause of DLK in clinical practice, but it is not known how endotoxin is transferred to the cornea. Endotoxin is a high-molecular-weight complex comprising lipopolysaccharide from the cell wall of gram-negative bacteria, which are ubiquitous. One investigation of a DLK outbreak found high levels of bacterial endotoxin in the sterilizer reservoir as a contaminating source.5 The endotoxin in the sterilizer reservoir may have been transferred to the LASIK instruments. Although steam sterilization is effective in killing bacteria, endotoxin may persist. The authors5 and those in another study6 recommend that the water reservoirs of sterilizers be emptied and changed weekly to prevent excessive growth of microorganisms and the formation of a biofilm that may contain high levels of endotoxin. The U.S. Food and Drug Administration's (FDA) Medical Device Reporting Program has received multiple reports of ophthalmic sponges as the suspected cause of DLK after LASIK. The program is a passive surveillance system that can prompt FDA investigations into potential health concerns. In 1 investigation, endotoxin testing of a sample of ophthalmic sponges from a lot associated with a DLK outbreak showed significantly higher levels of endotoxin than a sample of sponges not associated with DLK. The FDA has set bacterial endotoxin limits of 0.5 EU/mL for blood-contacting devices and 0.06 EU/mL for devices that make contact with spinal fluid. Endotoxin-free devices are usually labeled as nonpyrogenic or pyrogen free. Ophthalmic sponges for LASIK are not typically labeled pyrogen free. However, there are no bacterial endotoxin limits for ophthalmic sponges that may have high levels of endotoxin and cause DLK. Ideally, if ophthalmic sponges are the suspected cause of DLK, they should be assayed for endotoxin labels.7 Since most clinicians may not suspect a sterile ophthalmic sponge as a potential source of DLK-inducing endotoxin, the underreporting of this occurrence may be significant. Additionally, other reported causes in DLK cases in which the sponges are not considered a potential source of endotoxin may lead to nonfruitful pursuits. In the United States, the Safe Medical Devices Act (SMDA) of 1990 requires hospitals and other facilities to report to the FDA deaths and serious injuries associated with the use of medical devices. Laser in situ keratomileusis surgeons should follow the procedures established at their facility for such mandatory reporting. Reports may also be made through the voluntary reporting program, MedWatch. Reporting potential and actual device-related adverse events can stimulate targeted investigations and interventions that may reduce or prevent future occurrences. Reports can be submitted by telephone (1-800-FDA-1088), fax (1-800-FDA-0178), mail (MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, Maryland 20852-9787, USA), or online at www.fda.gov/medwatch/report.htm. To decrease the risk for a DLK outbreak, the following should be considered: (1) The water reservoirs in sterilizers should be changed at least weekly to prevent biofilm formation that can lead to endotoxin contamination on instruments. (2) Pyrogen-free devices should be used when available. Sterile does not mean endotoxin-free. (3) If an outbreak occurs, do not panic. Consider all possible sources and test those possibilities for the presence of endotoxin. (4) Report any device-related cases of DLK to the FDA, either through your facility or directly to MedWatch. Disclaimer: The opinions or assertions presented herein are the private views of the authors and are not to be construed as conveying either an official endorsement or criticism by the U.S. Food and Drug Administration. Joseph N. Blustein MD, MPH Victoria M. Hitchins PHD Eileen K. Woo RN Rockville and Silver Spring, MD, USA