In March, 2006, the Centers for Disease Control and Prevention (CDC) issued an alert warning of an increase in fungal keratitis eye infections nationwide that appeared to be linked to the use of Bausch & Lomb’s ReNu with MoistureLoc contact lens solution. As the CDC and other agencies continue the investigation, case studies from nationwide corneal disease centers may support the initial findings. To date, of the 130 cases of confirmed Fusarium keratitis, 125 have involved contact lens wearers. In addition, 75 of 118 individuals reported using only Bausch & Lomb's Renu with MoistureLoc, and 14 of 118 reported using MoistureLoc in combination with another product during the month before the onset of infection. The CDC has since disclosed that the use of Bausch & Lomb's ReNu with MoistureLoc during the month before the onset of keratitis was independently associated with corneal infection, and that this association was statistically significant (Morbidity and Mortality Weekly Report. May 19, 2006 / 55 (Dispatch);1-2). This article explores the experience of 1 laboratory center that managed a handful of suspicious keratitis cases during the outbreak and discusses the consequences of these findings.
The Problematic Fusarium Fungus
Fusarium sp. is an ubiquitous, filamentary fungus that gathers its nourishment from decaying organic matter, and in nature causes disease in plants. In the past decades there has been an emergence of infection by this microorganism in critically ill and immunocompromised individuals (J Med Microbiol. 2006;55(Pt 7):809-818). Fusarium sp has been an infrequent causative agent of keratitis, when compared with bacterial agents, because corneal infections with this microorganism have typically been associated with vegetable or organic matter that causes trauma to the eye. With the widespread use of contact lenses in the modern population, another mechanism of trauma to the corneal epithelium may have been inadvertently introduced. Even though fungal keratitis has historically been more prevalent in warm and tropical climates, in the past few years the southern states have seen an increase in its incidence (Am J Ophthalmol. 2006;142(1):154-155). Also, in temperate climates there has been an increase in filamentary fungal keratitis. In 2000 a report from Wills Eye Hospital revealed a series of 24 cases of fungal keratitis, in which 6 out of 24 isolates were Fusarium sp. This was second only to Candida sp. Of these 6 patients, 5 were identified as contact lens users (Cornea. 2000;19(3):307-312).
Clinically, the ophthalmologist should be aware of the characteristic appearance of fungal keratitis. Typically, the edges of the corneal ulcer are diffuse and feathery, and there may be multiple ulcers and even a ring infiltrate. In patients who have been receiving topical steroids, the full clinical picture may be masked, possibly due to a decrease in the local inflammatory reaction. These patients need to be observed very closely once the steroids are stopped.
Fusarium tends to infiltrate deep into the cornea early in the disease. There is some evidence that there is lack of a full inflammatory response in the cornea initially, which allows the fungus to penetrate deep into the tissue (Ophthalmology. 2002;109(8):1538-1546). One of the most feared complications of Fusarium keratitis is its penetration into the anterior chamber, where it can invade the lens and iris and form a “fungus ball” that mechanically occludes the pupillary area by creating a “keratomycotic malignant glaucoma” (Indian J Ophthalmol. 1991;39(3):118-121).
The Pittsburgh Experience
Between 1993 and August, 2005, a total of only 1 positive Fusarium culture had ever turned up on the contact lenses of patients at the University of Pittsburgh Medical Center (UPMC) Eye Center. Then between September 18, 2005, and April 19, 2006, 12 cultures that tested positive for Fusarium sp. were isolated from contact lens wearers who presented with clinically suspicious keratitis at this facility.
The best way to establish a diagnosis of Fusarium infection is through bacterial culture. Fusarium is not a fastidious grower and will appear as fuzzy colonies from 1 to 7 days after media inoculation at 30 degrees centigrade (C) or 37 degrees C incubation. Fusarium will also isolate on commonly used media such as Sabouraud agar, sheep blood agar, and thioglycolate broth. Antibacterial antibiotics such as gentamicin, chloramphenicol, or a penicillin-streptomycin combination can be added to the Sabouraud medium to prevent bacterial growth. A culture from both the cornea and the contact lens should be taken in order to maximize the chances of isolating the fungus. Direct examination of corneal smears may also be advantageous, because the results of a culture may take several days.
The data from the 12 aforementioned cases (Table 1) were reported to the CDC as part of an ongoing, multi-state investigation. Of the 12 total Fusarium isolates, 6 were found to be growing from patient corneas, and the lab returned negative cultures from the contact lenses of 2 of these patients. The remaining 6 patients were found to have Fusarium sp. growing in their contact lenses or lens cases. Four of these latter 6 patients tested negative for corneal fungi.