August 2009

 

OPHTHALMOLOGY NEWS

 

In the wake of Fusarium keratitis


by Maxine Lipner Senior EyeWorld Contributing Editor

 

 

Honing in on what led to the troubling outbreak

Fighting ocular infection...a new infection emerges Source: Francis Mah, M.D.

No one has forgotten the outbreak of Fusarium keratitis that occurred in users of soft hydrophilic contact lenses in 2006. We know that this was associated primarily with use of the ReNu MoistureLoc solution (Bausch & Lomb, Rochester, N.Y.), but what else have practitioners learned about this outbreak? That is what Arthur B. Epstein, O.D., Phoenix, set out to determine in a study published in the January 2009 issue of the Journal of Clinical Ophthalmology. “I think that this is a sensitive issue and obviously has significant corporate and financial repercussions, but this was a horrific experience for patients that shouldn’t go uninvestigated,” Dr. Epstein said. “There was a lot of pressure to look at this only from an infectious disease point-of-view.” The CDC [Centers for Disease Control and Prevention], together with Donald Tan, F.R.C.S., Singapore National Eye Center, Singapore, did a comprehensive job of compiling the salient data, but Dr. Epstein felt that nobody was cogently looking at what had allowed this to happen. “I wanted to establish a mechanism of action and essentially create a platform for people to start a dialogue,” he said.

Early on he found himself inadvertently entwined in the controversy. “Just by luck or sheer bad luck, I happened to be chair of the American Optometry Association contact lens and cornea section at the time that this hit,” he said. “I also do a fair amount of consulting so I have relationships with most of the industry. I was sort of at the epicenter of it all.”

Early clues

Prior to the outbreak, Dr. Epstein himself had stumbled on clues that there might be an infectious problem with the MoistureLoc solution. By early 2005 he had heard reports that patients were having surface issues with the new product with their silicone hydrogel lenses.

While he was out of town, he had his office manager soak eight or nine lenses in the solution. “I figured I would be back in a week or 10 days and I would examine the lenses to see if there was any interaction with the lens surface,” he said. “What I discovered was that about half of the cases had lenses that were covered in fungus.” When he showed pictures to some of his contacts in the industry, however, he was told that it had to be a fluke, or some sort of non-specific deposit, but certainly couldn’t be fungus. “I basically put it away and forgot about it until over a year later when I was reeling from overload and I said to my fiancée, ‘I wish that someone had figured this out earlier,’ and she said, ‘Well, you sort of did figure it out,’” Dr. Epstein said. The problem was that while the product had sailed through Food and Drug Administration (FDA) testing, which looked for the solution to maintain a certain level of disinfecting efficacy in the laboratory, in the real world it was a different story. In this case, several elements had to fall into place for there to have been a Fusarium outbreak. “No. 1, there had to be some means of ingress of these organisms,” Dr. Epstein said. “No. 2, there had to be some increase in the number of bacteria (in the eye), otherwise we wouldn’t have seen infections in North Dakota or Vermont in the winter.” The first cases, he points out, were in New Jersey, where fungal infections virtually never occurred previously. Thirdly, the product had to fail to disinfect—something which had to have occurred here. “We know that because we found the organisms that caused the infection,” Dr. Epstein said. “If the product had done its job there wouldn’t have been any organisms.”

Mulling over the mechanism

A potential mechanism for the outbreak currently being mulled over by the FDA is one of “uptake and release.” This would implicate the contact lens case system as an active player in the process of disinfection. “That’s one of the key takeaways from all of this,” Dr. Epstein said. In considering the uptake issue, Dr. Epstein notes that earlier work had shown that ReNu MultiPlus solution (Bausch & Lomb) lost its efficacy when soaked with certain contact lenses over a given period of time. “Basically the lens absorbed the disinfectant out of the solution in the case,” Dr. Epstein said. “So the organisms were free to grow.”

The theory is that with the Fusarium case, the disinfectant was pulled from the MoistureLoc solution by the lens material and then released into the tear film on the eye’s surface. “The tear film wasn’t designed to buffer high levels of disinfectant,” Dr. Epstein said. “So you end up with surface damage.” There is some basic chemistry to help explain this release. “The salt in the tear film is a releasing agent and helps the disinfectant release at relatively high levels,” Dr. Epstein said.

Lens material was also likely a key player here. “I think the reason we got into trouble is because our expectation is based upon conventional hydrogels,” Dr. Epstein said. “We’ve used conventional hydrogels for years, and patients would use tap water, homemade saline, hospital saline, and stuff that would boggle the imagination, with filthy, disgusting cases and never get any infections.” Indeed Fusarium notwithstanding, background infections have also risen in recent years. “There is evidence from Wills [Eye Hospital, Philadelphia] that infections associated with contract lens wear went up 2.5 times starting in 1999,” he said. “I think part of the problem is that the chemistry of silicone hydrogels is so different from conventional hydrogels that it caused some major issues for the solution manufacturers.”

Going forward, Dr. Epstein thinks that the FDA will need to begin testing under real world conditions, using lenses and cases, to ensure that kill curves are maintained. “At the same time, they’re probably going to need to look at corneal staining grades to make sure that there’s not a lot of release back into the tear film, which can disturb the surface,” Dr. Epstein said. He hopes that practical safety standards can soon be developed. “My biggest fear is that this becomes a political or corporate issue and it interferes with promulgating new standards that will provide patients with reasonable safety,” Dr. Epstein said. “Conversely, I’m concerned that the standards might be so high that it would be impossible for manufacturers to meet them.” He believes that the middle ground is very important to reach. “I think that we owe it to our patients, especially the ones who suffered, to make sure that we learn from this,” he said.

Editors’ note: Dr. Epstein has financial interests with Alcon (Fort Worth, Texas).

Contact information

Epstein: 480-626-0988, artepstein@artepstein.com