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Contact lens solution is focus of fungal keratitis investigation
As the CDC focused attention on a Bausch & Lomb contact lens cleaning solution, the company asked U.S. retailers to take the product off their shelves.
Health care providers are being asked to culture patients when they present with microbial keratitis and to consider the possibility of a fungal infection in those patients, in the wake of reports of fungal keratitis in the United States.
The recent spate of corneal Fusarium infections in soft contact lens wearers has led to corneal transplants in eight patients, according to a report from the Centers for Disease Control and Prevention.
Reports of soft contact lens-related fungal keratitis infections, clustered first in areas of East Asia and subsequently in parts of the United States, initially baffled the ophthalmic community and put physicians on alert for the rare but potentially vision-threatening condition.
Subsequent investigation by the CDC has resulted in a focus on a particular contact lens care solution manufactured by Bausch & Lomb, according to information released by the CDC and Bausch & Lomb.
The link between lens care solution and the infections is not definitive, the CDC and Bausch & Lomb noted.
On April 10, Bausch & Lomb released a statement saying that the company was temporarily suspending U.S. shipments of its ReNu with MoistureLoc lens care solutions produced in its Greenville, S.C., manufacturing facility. That product generated about $45 million in U.S. sales in 2005, according to the company.
In another statement 3 days later, the company took a further step, asking U.S. retailers to take the ReNu with MoistureLoc off their shelves temporarily and asking consumers to switch to another lens care solution for the time being.
B&L stated in a press release on April 13 that “nothing has yet been found to show that ReNu with MoistureLoc contributed to these infections in any way,” but the company undertook the voluntary market withdrawal “in order to eliminate any confusion among contact lens wearers about what to do while the investigation is ongoing.”
The company also placed full-page advertisements in major U.S. newspapers on Sunday, April 16, with a similar message for consumers and answers to frequently asked questions.
Culture positive Fusarium corneal ulcer in a contact lens wearer showing characteristic hazy white flocculent appearance with fuzzy margins. Images: University of Iowa |
Disproportionate representation
“There is an apparent disproportionate representation of U.S. manufactured ReNu with MoistureLoc in the underlying data,” said B&L chairman and chief executive officer Ronald L. Zarrella, commenting on the CDC report on the Fusarium infections in the April 10 B&L press release. “The available scientific evidence does not establish any type of ReNu solution as a cause.”
Fusarium keratitis, a rare fungal infection, is normally associated with a plant fungus or vegetation-related trauma to the eye. It is most common in warm climates and rural areas. But even in those areas, the condition is uncommon.
“Most ophthalmologists, in their entire careers, never see even one case of fungal keratitis,” said Penny A. Asbell, MD, FACS, OSN Editorial Board Member.
On March 8, the CDC received a report from an ophthalmologist in New Jersey who had seen three patients with Fusarium keratitis in the course of 3 months.
Between that date and April 10, the CDC received reports of 109 cases of suspected Fusarium keratitis in 17 states: California, Connecticut, Florida, Georgia, Iowa, Maryland, Massachusetts, Michigan, Missouri, New Jersey, New York, North Dakota, Ohio, Pennsylvania, Tennessee, Texas and Vermont.
On April 10, the CDC’s Morbidity and Mortality Weekly Report released an MMWR Dispatch describing the situation to that date. The report said the CDC, the Food and Drug Administration and public health authorities were still investigating the situation.
The investigation is intended to determine “ whether this cluster represents an increase of Fusarium keratitis infections and to determine the association, if any, of these cases with any product,” according to the MMWR report.
The dispatch noted that of the 109 patients with suspected Fusarium keratitis, most have not been interviewed. But in the 30 patient cases that had been fully investigated, 28 patients (93%) reported wearing soft contact lenses. Two patients reported no contact lens use.
Of the 28 patients who wore soft contact lenses, 26 (93%) remembered what contact lens solution they had used in the month before the onset of infection or still had the original bottle. Of those 26 patients, all 26 reported using Bausch & Lomb ReNu brand contact lens solution or a generic product manufactured by the same company, according to the dispatch from the MMWR.
Press releases from Bausch & Lomb regarding the situation have not included any statements regarding generic solutions manufactured by the company.
According to the MMWR report, patients reported using a number of different ReNu product types from different product lots. Five patients (18%) reported using other brands of solutions in addition to the ReNu, including products from Advanced Medical Optics and Alcon.
Nine patients reported wearing lenses overnight, which the MMWR noted is a known risk factor for microbial keratitis. To date, eight patients have required corneal transplants, according to the MMWR report.
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Earlier reports in Asia
Reports of unusual cluster of Fusarium keratitis reports surfaced as early as last year from health authorities in Hong Kong, Singapore and Malaysia.
On March 31, Bausch & Lomb announced that it had undertaken collaborations with health officials in Hong Kong and Singapore to find possible causes of the fungal keratitis cases that were reported there as early as November 2005.
Health officials in Singapore and Hong Kong had reported that most affected patients reported using Bausch & Lomb’s ReNu multi-purpose lens care solution.
A Bausch & Lomb press release on March 31 stated, “When the first reports of the unusual spike in contact lens-related Fusarium keratitis in Singapore and Hong Kong first came to the attention of Bausch & Lomb, the company immediately suspended sales of ReNu multi-purpose solutions there and initiated an extensive series of additional tests on the sterility and biocidal efficacy of its products. The results have yielded no evidence to suggest that the products in any way caused or contributed to the infections. Moreover, health authorities in Hong Kong and Shanghai reported that their independent tests of samples of ReNu multi-purpose solutions obtained in those markets confirmed that the products are sterile.”
The following week, a press release from Bascom Palmer Eye Institute announced that a “sudden increase in the number of cases” had been reported in parts of the United States, as well as in the Asia-Pacific region.
B&L has stated that the Asian regions where clusters of infections were reported are all served by its U.S. manufacturing plant. In other markets, including Europe, China and India, the ReNu with MoistureLoc product is made in other factories, and no unusual trends in Fusarium infections have been reported there.
Rising numbers
Dr. Asbell said her practice in New York has seen three cases of fungal keratitis in 2006. In one case, a 20-year-old male patient was referred to her office with what was originally thought to be a more common bacterial infection.
“I started seeing him mid-February. Other doctors were trying different treatments and not getting anywhere,” she said. “I thought, has anybody thought it might be fungal?”
Cultures confirmed that the patient’s infection and vision problems were caused by fungal infection. His vision progressed to hand motions, and then the cornea perforated. He progressed to corneal transplant, Dr. Asbell said, and he is now recovering.
The other two cases in her practice have been successfully treated medically, she said.
“Two cases is not enough to necessarily raise a red flag, but then I got a health announcement from the state of New Jersey, saying a New Jersey physician had three cases of contact-lens related fungal infections,” Dr. Asbell said in a telephone interview with Ocular Surgery News.
Dr. Asbell said eye care professionals should be aggressively diagnosing all corneal abnormalities and considering fungal keratitis in patients who wear soft lenses.
A Bascom Palmer press release reported that, between 2000 and 2005, the average number of cases of Fusarium keratitis seen per year at its Miami facility was 21, and less than 2% of those cases involved contact lens wearers. Between January and March 2006, Bascom Palmer has seen 21 cases, of which 12 were contact lens wearers.
Dr. Asbell commented, “In Florida, there may be more cases with the warm climate. You do see fungal infections. But in the Northeast it is rare, and very rare when not related to trauma. A fungal ulcer in a 20-year-old healthy person is extremely rare in New York City.”
A spokesman for the American Academy of Ophthalmology, Thomas L. Steinemann, MD, said, “Fungal keratitis infections are not common in most practices, particularly in the setting of soft contact lens wear. I am working with Academy members to get a sense of how big of a problem this is. At this point, we just don’t know.”
Diagnosing, treating infections
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Dr. Asbell said she has emphasized to residents that if they see a contact lens patient with symptoms of irritation, they should consider fungal infection in the differential diagnosis.
She said she is also taking time to educate her contact lens patients about the importance of reporting redness or irritation as soon as possible.
“I have told my patients that there is a problem with infections, and we’re not sure why,” she said. “If something happens, you want to be able to make the diagnosis as soon as possible.”
A fungal infection in the cornea can be more indolent than a faster-moving bacterial infection, which would typically be treated with antibiotics, Dr. Steinemann said.
“Most likely patients will still present with redness, pain and light sensitivity,” he said. “If you see someone with a soft-contact-lens-related red eye, normally you would most likely treat it with antibiotic drops. You would probably not empirically start someone on an antifungal. It’s important to remember that antibiotics are not going to be of any benefit and could delay proper treatment, allowing the fungal infection to become more deep-seated.”
If a fungal infection is suspected, Dr. Steinemann said, a culture should be taken.
“Smaller clinics and private offices probably do not routinely culture corneal ulcers,” Dr. Steinemann said.
Dr. Asbell said voriconazole is “particularly good” against Fusarium keratitis. Marketed as Vfend by Pfizer, voriconazole is formulated for oral and intravenous delivery for treatment of fungal infections,. Dr. Asbell said she had a compounding pharmacy make it into an eye drop for one of the patients in her practice.
Another FDA-approved antifungal is Natacyn (natamycin ophthalmic suspension 5%, Alcon), Dr. Asbell said.
Industry-wide awareness
Spokespersons for Advanced Medical Optics, Alcon and CIBA Vision said the companies are aware of the recent reports of fungal keratitis and are monitoring the situation.
Ralph Stone, PhD, vice president of clinical affairs for Alcon, noted that none of the reported fungal keratitis cases in Hong Kong, Singapore or Malaysia were related to the use of Opti-Free Express or Opti-Free Replenish multipurpose solutions.
Steve Chesterman, manager of corporate communications for AMO, said that the recent infections prompted AMO to review data regarding its Complete line of multipurpose solutions. The review confirmed its safety, he said.
CIBA Vision officials said they are aware of the reports of fungal keratitis, but there has not been an increase in reported cases among consumers who use their lenses and lens care products.
For more information:
- Penny A. Asbell, MD, FACS, can be reached at Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1183, New York, NY 10029; 212-241-7977; fax: 212-241-7977.
- Thomas L. Steinemann, MD, can be reached at MetroHealth Medical Center/Ophthalmology, 2500 MetroHealth Drive, 3rd Floor, Cleveland, OH 44109; 216-778-4253; fax: 216-778-7863.
- Ralph Stone, PhD, vice president of clinical affairs for Alcon, can be reached at 6201 S. Freeway, Fort Worth, TX 76134-2099; 817-293-0450.
- Steve Chesterman, manager of corporate communications for Advanced Medical Optics, can be reached at 1700 E. St. Andrew Place, P.O. Box 25162, Santa Ana, CA 92799-5162; 714-247-8200; fax: 714-247-8680.
- Lisa Gilbert, senior manager of corporate communications at CIBA Vision, can be reached at 11460 Johns Creek Parkway, Duluth, GA 30097; 678-415-3937.
References:
- Barry MA, Pendarvis, J, et al. Fusarium keratitis — Multiple states, 2006. MMWR Morb Mortal Wkly Rep. 2006, Apr 10;55:1-2.
- Bausch & Lomb can be reached at One Bausch & Lomb Place, Rochester, NY 14604-2701; 585-338-6000; fax: 585-338-6007; www.bausch.com
- Daniele Cruz is an OSN Staff Writer who covers all aspects of ophthalmology.
- Jennifer Byrne is an OSN Correspondent who works principally for OSN’s sister publication, Primary Care Optometry News.