The five cases of contact lens– related Fusarium keratitis diagnosed last winter by ophthalmologists at the Baylor College of Medicine did not initially arouse much concern. “In retrospect, we here at Baylor noticed a little uptick of contact lens-related fungal infections,” said Dan B. Jones, MD, professor and chairman of the school’s ophthalmology department. “We paid attention, but didn’t understand it and didn’t launch any investigation of our own.” In fact, few people saw the significance of the increase in Fusarium. “Before June 2005, contact lens Fusarium keratitis was an oddity.”
That was about to change. “All of a sudden,” said Dr. Jones, “we realized this was an unusual event.” It was, as he put it, “a true mystery outbreak.” Within months, he and other experts, along with the CDC and FDA, were caught up in an investigation, trying to track down the source of the fungal infection. By June 2006, the CDC had reported 130 confirmed cases (125 related to contact lenses), and Bausch & Lomb had voluntarily withdrawn its contact lens solution, ReNu with MoistureLoc, from worldwide distribution because so many of the infected patients had used it. But if ReNu with MoistureLoc was the culprit (which wasn’t proved), nobody knew why. “There’s something that’s different here that we don’t understand,” Dr. Jones said.
Another bug, another outbreak. Over the same approximate period of time, doctors at Wills Eye Hospital were seeing an unusual number of cases of a contact lens–related infection caused by Acanthamoeba, a protozoan typically associated with water sources.
Acanthamoeba keratitis, a sight-threatening infection of the ocular surface, has been described as producing “exquisite pain and ulceration of the ocular surface.”1 The infection is usually initiated by contaminated contact lenses. Like the Fusarium infections, it’s usually considered rare.
Kristin M. Hammersmith, MD, had seen one or two cases of Acanthamoeba keratitis during her fellowship training at Wills in 2002–2003. In 2004, she saw 10. “Then we kept seeing them in 2005,” said Dr. Hammersmith, the cornea fellowship director at Wills Eye Hospital and instructor of ophthalmology at Thomas Jefferson University. The Wills outbreak, which she reported at the Academy’s 2005 Annual Meeting, involved 20 cases diagnosed between January 2004 and November 2005.
Other groups were reporting an upsurge, too. “There’s been a chronic problem. And now we have an acute problem on top of that,” Dr. Hammersmith said. “It’s concerning to have so much infection related to contact lenses.”
Corneal infections among the 30 million U.S. contact lens wearers are not unusual. Most, however, are associated with bacteria and careless lens care practices, which is why researchers have puzzled over two nearly simultaneous and rare outbreaks due to a fungus and a parasite.
At the ARVO meeting this spring, one presenter speculated that an outbreak of Acanthamoeba keratitis in Chicago might have been caused by a relaxation in EPA regulations governing the decontamination of tap water.
Among the 20 cases diagnosed at Wills, there was a higher incidence of infection among patients who swam with their lenses on or who were exposed to well water. (At first, the Wills group hadn’t focused on multipurpose lens solutions, but after the Fusarium outbreak they went back and found that nine of the 15 patients for which data exist used ReNu products, though not necessarily MoistureLoc.)
Yet 30 percent of the Wills cases had no unusual history, suggesting that Acanthamoeba keratitis could occur, despite apparently proper use of frequent replacement contact lenses and multipurpose solutions. “They were normal, compliant contact lens wearers,” Dr. Hammersmith said. But the solutions available to wearers may not be sufficiently microbicidal. “None of the multipurpose solutions are effective for these uncommon organisms.”
And more theories. Fusarium investigators were homing in on the lens solution as the source of the outbreak. But by early June, Dr. Jones had more questions than answers. “Why Fusarium and not some other organism?” he wondered. And if the outbreak is related to ReNu with MoistureLoc, which has been available since 2004, why did the outbreak occur now? By mid-May, the lens solution had been used in 64 percent of the contact lens–related cases. Another 12 percent reported using it in combination with another product. Still, 18 percent reported using only products other than MoistureLoc.
Certain variables were ruled out. “Ophthalmologists and corneal practices haven’t suddenly improved their clinical recognition,” Dr. Jones said. And the lens material hadn’t changed. “You have to infer that something else happened,” he continued. “Is it some environmental factor?”
Investigators looked at everything from global warming to a delayed reaction to the last hurricane season, when a huge amount of vegetation was destroyed and then burned or ground up. Dr. Jones, who served as an expert to Bausch & Lomb during the outbreak, said that it may sound “far-fetched,” but the vegetation could have been contaminated with Fusarium, then become airborne and created a greater risk factor for contamination of water and other surfaces.
Or perhaps there was something different about ReNu with MoistureLoc? On May 16, Ronald L. Zarella, Bausch & Lomb’s chairman and CEO, told reporters that an eye comfort-enhancing polymer unique to the formulation might form around the fungus, protecting it from the disinfectant.
Even if that turns out to be the answer, Dr. Jones’ question remains. Why is Fusarium the culprit? Is there any significant environmental factor about Fusarium that’s different? “So far, that’s not been answered.”
Through a Lens, Darkly
Despite the nagging questions, Dr. Jones was sure of one thing. He said the FDA should establish new guidelines and stricter requirements for approving contact lens solutions. “Here was a product judged to be safe. Obviously, there was no test methodology that suggested that what happened might have happened.”
What’s more, ophthalmologists need a better, clearer reporting system, he said. Though the Fusarium outbreak was first reported in Singapore last winter, it was only after a New Jersey ophthalmologist reported three cases that the story finally broke, months later, in the United States. “It’s regrettable,” Dr. Jones said, “that it took a whole crescendo of cases before it bubbled to the public awareness. Even now, patients are coming in using ReNu with MoistureLoc.”
|Diagnosis, Treat, Prevent |
It’s hard to prevent an infectious outbreak from spreading when the source is unknown. But even while the sleuths are at work, infected patients need to be treated. Here’s what the experts advise.
Suspect the worst and don’t delay. Have a higher index of suspicion of unusual infections in soft contact lens wearers. “These infections can present as looking like a bacterial infection, especially Fusarium,” said Christopher J. Rapuano, MD, codirector of the cornea service, Wills Eye Hospital, and professor of ophthalmology, Thomas Jefferson University. Nearly three-fourths of the Wills Acanthamoeba patients had been misdiagnosed earlier as having herpes simplex virus (see Fig. 1). Patients who were diagnosed early did better.
Avoid steroids. Steroids are often prescribed in conjunction with antibiotics to treat microbial infection. But they can complicate recovery from Fusarium and Acanthamoeba infection. “Doctors need to be very careful about using that same treatment philosophy now. If it’s Fusarium or Acanthamoeba, the steroids actually promote the infection,” Dr. Rapuano
Educate other patients. If you think well water or swimming with contacts in is the cause, then reinforce that message.p>
Recommend single-use, daily-wear disposable lenses. Or use a disinfecting solution with the longest possible exposure to hydrogen peroxide.p>
Treat Fusarium keratitis with natamycin drops. These are usually applied hourly during the day. Other antifungal agents may be used.p>
Treat Acanthamoeba infection with a combination of PHMB (specially prepared Baquacil pool disinfectant) drops, propamidine (Brolene, obtained from outside the United States) drops, and often Neosporin ophthalmic drops, frequently around the clock. It may also treated with oral medications such as itraconazole. Patients typically need oral pain medication.
Be vigilant and report. Report possible cases to state health departments, the CDC at 800-893-0485, and the FDA via MedWatch at 800-332-1088.
1 Clarke, D. W. and J. Y. Niederkorn. Trends Parasitol 2006;22(4):175–180.
Drs. Hammersmith and Jones report no related financial interests. Dr. Rapuano is on the lecture board for Allergan and Alcon.