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

PURPOSE: A root cause analysis of the Fusarium keratitis epidemic of 2004-2006 was performed.
METHODS: Three 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.
RESULTS: The 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.
CONCLUSIONS: The 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.