Root cause analysis of the fusarium keratitis epidemic of 2004-2006 and prescriptions for preventing future epidemics.

purposeA root cause analysis of the Fusarium keratitis epidemic of 2004-2006 was performed.

methodsThree US Food and Drug Administration (FDA) documents were analyzed. Poisson and case-control studies were performed on outbreak data from Singapore. Irreversible thermochromic labels were applied to cartons of contact lens solution bottles, which were then subjected to elevated temperatures.

resultsThe 1997 FDA guidance document concerning storage temperatures of contact lens care products predicted temperature-related solution instability. Bausch & Lomb (B&L) requested FDA approval for ReNu with MoistureLoc, claiming that it was substantially equivalent to other products. FDA Form 483 stated that cases of ReNu-related Fusarium keratitis from Asia had not been reported, the removal of the product from the Asian markets was unreported, and B&L had not performed biocidal testing on samples associated with Asian cases. The outbreak in Singapore could have been recognized after only 3 cases (Pr = .0067). The cause of the Singapore outbreak could have been determined after the recognition of only 3 (P = .0429), 5 (95% confidence interval [CI], 1.15-126.0), or 15 cases (95% CI, 1.60-14.1). Thermochromic labels can irreversibly change color when exposed to elevated temperatures, thus warning of potential antimicrobial failure.

conclusionsThe worldwide Fusarium keratitis epidemic of 2004-2006 could, theoretically, have been prevented entirely, recognized much earlier, or mitigated by much more rigorous oversight by the FDA, by strict adherence by B&L to FDA guidelines and requirements, by the application of basic statistical methods, and/or by the use of temperature indication technology. The lessons learned from a root cause analysis of this pharmacologic catastrophy may help avert or mitigate future epidemics.