On March 8, 2006, the Centers for Disease Control and Prevention (CDC) received a report from an ophthalmologist in New Jersey regarding three patients with contact lens–associated Fusarium keratitis during the preceding 3 months. Initial contact with several corneal disease specialty centers in the United States revealed that other centers also have seen recent increases in Fusarium keratitis. This report summarizes the public health response to date in the United States and provides important prevention messages for contact lens users.
Microbial keratitis is a severe infection of the cornea. Risk factors for infection include trauma (generally with plant material), chronic ocular surface diseases, immunodeficiencies, and rarely, contact lens use (1–3). An estimated 30 million persons in the United States wear soft contact lenses; the annual incidence of microbial keratitis is estimated to be 4–21 per 10,000 soft contact lens users, depending on whether users wear lenses overnight (4). Fungal keratitis is a condition more prevalent in warm climates; in the southernmost United States, up to 35% of microbial keratitis cases are fungal keratitis, compared with 1% in New York (5,6). The proportion of fungal keratitis attributable to Fusarium spp. also varies by region, from 25% to 62% (1,2,5). First-line treatment includes topical and oral antifungal medications; patients who do not respond to medical treatment usually require surgical intervention, including corneal transplantation (3). Fusarium keratitis is not transmitted from person to person.
As of April 9, 2006, a total of 109 patients with suspected Fusarium keratitis were under investigation in multiple states. Case finding was conducted through postings on the Epidemic Information Exchange (Epi-X) and ophthalmology listservs and through queries of clinical microbiology laboratories. CDC is coordinating an investigation with public health authorities in California, Connecticut, Florida, Georgia, Iowa, Maryland, Massachusetts, Michigan, Missouri, New Jersey, New York, North Dakota, Ohio, Pennsylvania, Tennessee, Texas, and Vermont. The majority of patients have yet to be interviewed; however, of 30 patients for whom complete data were available, the median age was 48 years (range: 13–83 years), and 21 (70%) were female; infection onset occurred during June 15, 2005–March 18, 2006.
Twenty-eight patients (93%) wore soft contact lenses, and two (7%) reported no contact lens use. Among contact lens users, 26 (93%) remembered which solution they used during the month before infection onset or had retained the actual bottle. Of these, 26 (100%) reported using a Bausch & Lomb (Rochester, New York) ReNu® brand contact lens solution or a generic-brand solution manufactured by Bausch & Lomb. Patients reported using various ReNu product types from multiple product lots. Five (18%) patients reported using other solutions in addition to the ReNu solution, including solutions made by Advanced Medical Optics, Inc. (Santa Ana, California) and Alcon (Fort Worth, Texas). Nine (32%) patients reported wearing contact lenses overnight, a known risk factor for microbial keratitis. Eight (29%) required corneal transplantation. Laboratory testing to evaluate product contamination, including typing of Fusarium spp. isolates, is ongoing.
Clusters of Fusarium keratitis were reported among contact lens users in Asia beginning in February 2006. At that time, Bausch & Lomb voluntarily suspended sales of its ReNu multi-purpose solutions in Singapore and Hong Kong, pending investigation, after multiple reports of Fusarium keratitis among contact lens users there (7).
An ongoing investigation by CDC, state and local health departments, and the Food and Drug Administration is under way 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. Epidemiologic and laboratory studies will help define specific activities, hygiene practices, or products that place persons at increased risk for Fusarium keratitis.
Measures to reduce the risk for microbial keratitis can be instituted immediately by contact lens users and include the safe handling, storage, and cleaning of contact lenses. Specifically, contact lens users should:
- wash their hands with soap and water and dry them before handling lenses,
- wear lenses according to the schedule prescribed by eye-care practitioners and solution manufacturers, and
- follow guidelines for cleaning and storing lenses provided by eye-care practitioners and solution manufacturers.
Contact lens users with questions about which solutions are best for them should consult their eye-care professionals and carefully weigh risks and benefits.
Clinicians evaluating contact lens users with signs or symptoms of keratitis, such as unusual redness, eye pain, tearing, discharge, or sensitivity to light, should consider fungal keratitis and refer the patient to an ophthalmologist, if appropriate. Clinicians should consider obtaining clinical specimens (e.g., corneal scrapings) for culture before initiating treatment. Clinicians or microbiology laboratories should report cases of Fusarium keratitis to state and local health departments or directly to CDC at telephone, 800-893-0485. Fusarium isolates should be submitted to state laboratories according to instructions provided by local and state public health laboratories.
References available on the CDC site.
The U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) are alerting health care professionals and their patients who wear soft contact lenses to an increasing number of reports in the United States of rare but serious fungal infections in the eye that can cause permanent loss of sight. Some patients have reported a significant loss of vision, resulting in the need for a corneal transplant.
A fungus called Fusarium has been identified as the cause of the reported infections. As of April 9, 2006, 109 cases of suspected Fusarium keratitis are under investigation by CDC and public health authorities in 17 states of the U.S.
“This is a serious infection and soft contact lens users should be mindful of the potential to develop this problem,” said Dr. Daniel Schultz, director of the FDA’s Center for Devices and Radiological Health. “We’re advising consumers to practice good basic hygiene and follow manufacturers’ instructions for proper use, cleaning and storage of their lenses, and report any signs of infection to their doctors.”
Clinicians who evaluate patients with microbial keratitis should consider that a fungal infection may be involved and refer the patient to an ophthalmologist, if appropriate to obtain a specimen for laboratory analysis. In addition, the FDA and CDC are urgently advising consumers to take precautions to prevent contamination of the soft lenses and the products used to maintain them. These preventive practices for contact lens wearers include the following:
In addition, regardless of which cleaning/disinfecting solution used, wearers may want to consider performing a “rub and rinse” lens cleaning method, rather than a no rub method, in order to minimize the number of germs and reduce the chances of infection.
Fusarium species are normally found in many plants, soil, and tap water. The annual risk of contact lens-related microbial keratitis is estimated in most studies to be between four and 21 per 10,000 patients, depending on whether the lenses are worn only during the day or continuously overnight.
Fungal keratitis can be associated with trauma to the surface of the eye, immunodeficiencies, and contact lens use. Organisms associated with contact lens-related keratitis are usually bacteria rather than fungus, often arising from contamination of lens care products or from contact lens storage cases.
Additional information is available on FDA’s website:
Public Health Notice: http://www.fda.gov/cdrh/safety.....titis.html
Peter
________________
Dr Peter Tylee
Editor
FDA Update: April 21, 2006
New Information
On April 13, 2006, Bausch and Lomb announced that it is withdrawing all ReNu with MoistureLoc products and is recommending that consumers stop using ReNu with MoistureLoc immediately.
Both the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) continue to investigate reports of fungal keratitis in an effort to determine all contributing factors and/or products that place contact lens wearers at increased risk for Fusarium keratitis.
Updated Recommendations
For healthcare providers:
For contact lens wearers:
FDA Advice to Patients on this topic can be found here.
Peter
________________
Dr Peter Tylee
Editor
Today, FDA is providing the latest update about soft contact lens use and contact lens solution that may increase the risk for Fusarium keratitis. This update is intended to clarify recently released information on cases of Fusarium keratitis associated with contact lens solution.
Update on Serious Eye Infections Associated With Soft Contact Lens Use and Contact Lens Solution — May 5, 2006
As reported by CDC, patients with confirmed cases of Fusarium keratitis have reported using various contact lens cleaning solutions including various types of ReNu products and generics. We continue to confirm reported cases associated with products other than ReNu with MoistureLoc. Our interest in the MoistureLoc product is based on the disproportionate number of case of Fusarium keratitis associated with ReNu with Moisture Loc compared to the overall product market share. The trends of reported cases involving various contact lens solutions other than MoistureLoc have remained consistent throughout our investigation.
FDA continues to work with the CDC to investigate the Fusarium keratitis infections and will determine whether or not further action needs to be taken. While the investigation is ongoing, FDA will continue to update the public health notice and advice to consumers as needed. In addition, the FDA and CDC are urgently advising consumers to consult your doctor immediately if you experience symptoms such as redness, pain, tearing, increased light sensitivity, blurry vision, discharge or swelling. In addition, the Centers for Disease Control and Prevention (CDC) released further clarification on the information on the multi-state outbreak of Fusarium keratitis that may be associated with contact lens use.
A full update from the CDC is available here.
Peter
________________
Dr Peter Tylee
Editor
A new site provided by the FDA will be of interest to all contact lens wearers. More details are here.
Peter
________________
Dr Peter Tylee
Editor
May 15, the Food and Drug Administration (FDA) issued Bausch & Lomb a report detailing its observations at the conclusion of the inspection of the Greenville, SC plant and a related facility as part of an investigation into a recent increase in Fusarium keratitis infections associated with contact lens wearers using the ReNu with MoistureLoc contact lens cleaning solution. Inspectional Observations (FDA 483) issued by the agency details the investigator’s observations that were found to deviate from FDA quality system regulation.
On March 22, 2006 investigators from the FDA’s Atlanta District Office began inspections of Bausch & Lomb’s Greenville, SC manufacturing plant and a related facility to identify any possible source of Fusarium. During the inspection, FDA and the Centers for Disease Control and Prevention (CDC) conducted extensive sampling and testing as part of the joint investigation. Preliminary results to date from testing of environmental factors, raw materials, in-line manufacturing processes and finished products have not found that these factors have contributed to Fusarium contamination. Laboratory testing is ongoing.
Bausch & Lomb has proposed the ReNu with MoistureLoc formulation as the potential root cause of the increased relative risk of Fusarium keratitis. The observations from the FDA inspection, which may indicate deviations from current good manufacturing practice, do not necessarily support a connection between the formulation of the ReNu with MoistureLoc product and the Fusarium keratitis infections.
It is important to point out FDA’s inspectional observations are preliminary and will need to be further evaluated before any conclusions can be drawn about such a connection. It is premature to conclude that some of the observations cited in the report are associated with the cases of Fusarium keratitis. Once the Establishment Inspection Report (EIR) is written, and documentation reviewed, FDA will be in a better position to evaluate its options.
The following update is from the MMWR Dispatch May 19, 2006 / 55(Dispatch);1-2.
In April 2006, CDC reported on an ongoing multistate investigation of Fusarium keratitis occurring predominantly among contact lens wearers (1). This update summarizes epidemiologic developments in this investigation, which indicate an association with Bausch & Lomb’s ReNu with MoistureLoc® contact lens solution.
Fusarium keratitis is a fungal infection of the cornea, preceded usually by trauma to the eye. Although not a notifiable disease, the infection is thought to be rare among contact lens wearers in temperate climates (2). Fusarium keratitis is treated with antifungal medication but can be severe and sometimes result in vision loss and the need for corneal transplantation (3).
As of May 18, 2006, CDC had received reports of 130 confirmed cases of Fusarium keratitis infection, defined as clinically consistent fungal keratitis with symptom onset after June 1, 2005, no history of recent ocular trauma, and a corneal culture yielding a Fusarium species. Cases have been reported from 26 states and one territory.* Patients had a median age of 41 years (range: 12–83 years), and 85 of 127 (67%) were female. As a result of this infection, corneal transplantation was required in 37 of 120 (31%) cases.
Among the 130 patients with confirmed cases, 125 reported wearing contact lenses, and 118 were able to identify which contact lens solution(s) they had used during the month before onset of infection. Seventy-five (64%) reported using Bausch & Lomb’s ReNu with MoistureLoc alone, 14 (12%) reported using MoistureLoc in combination with another product, eight (7%) reported using an unspecified Bausch & Lomb solution, and 21 (18%) reported using only products other than MoistureLoc, from various manufacturers. Ongoing surveillance continues to identify persons who used MoistureLoc and had disease onset after April 13, when Bausch & Lomb withdrew this product from the market in the United States.
In April, a subset of confirmed case-patients who were soft contact lens wearers and aged >18 years was enrolled in a matched case-control investigation to evaluate risk factors for infection. To avoid potential bias from media coverage on case-patient responses, this subset was limited to those patients reported to CDC before online publication of the initial MMWR Dispatch on April 10. Neighborhood-matched controls were adults reporting soft contact lens use during March 2006 with no history of fungal keratitis. Information regarding contact lens types, solutions used, and contact lens hygiene practices was obtained via telephone interviews conducted by trained personnel who used standardized questionnaires. Exact conditional logistic regression was used to estimate odds ratios.
A total of 50 case-patients and 79 controls were enrolled in the matched case-control investigation. For the most stringent test of product association, analysis was limited to the matched sets of 25 case-patients and 37 controls who were soft contact lens wearers, reported using only a single solution type, and provided all the information requested. In a multivariable model, use of Bausch & Lomb’s ReNu with MoistureLoc during the month before symptom onset was independently associated with being a case-patient (adjusted odds ratio: 19.0, 95% confidence interval = 2.4–944.9, p<0.001), when compared with contact lens solutions other than ReNu with MoistureLoc or ReNu Multiplus®; 19 case-patients and seven controls reported this exposure. This association was statistically significant even after controlling for poor contact lens care (i.e., reported reuse or topping off of contact lens solution). Use of ReNu Multiplus solution was not significantly associated with infection (adjusted odds ratio: 3.6, 95% confidence interval = 0.3--189.0, p = 0.5); five case-patients and 10 controls reported this exposure.
The results of this case-control investigation indicate an increased risk for Fusarium keratitis associated with use of Bausch & Lomb's ReNu with MoistureLoc. The cause of this association is not clear; however, further studies, including environmental and molecular testing, are ongoing. Although certain patients have reported use of other contact lens solutions, the analysis does not indicate that these products are associated with significantly increased risk for disease. Patients who reported using only products other than MoistureLoc might not have recalled all the contact lens solutions they had used, especially if the period between exposure and interview was lengthy. In addition, extensive surveillance for this infection might have identified patients whose disease was unrelated to the outbreak.
Given the association between Fusarium keratitis and MoistureLoc, Bausch & Lomb (Rochester, New York) announced its decision to voluntarily recall and permanently remove this contact lens solution from the worldwide market on May 15, 2006. Contact lens wearers should immediately discontinue use of this solution and consult an eye-care professional regarding use of an appropriate alternative product for cleaning or disinfecting lenses. Contact lens wearers also should practice good hygiene, including hand washing and drying before handling lenses, avoiding reuse of contact lens solutions, and following the specific instructions of manufacturers of contact lenses and contact lens solutions. Clinicians evaluating contact lens wearers with signs or symptoms of keratitis (e.g., unusual redness of the eyes, eye pain, tearing, discharge, or light sensitivity) should consider fungal keratitis and refer the patient to an ophthalmologist if appropriate. Eye-care professionals should continue to be vigilant in the diagnosis and treatment of Fusarium keratitis, and should report possible cases to state health departments or to CDC at telephone, 800-893-0485. Reports should also be submitted to the FDA via MedWatch at telephone, 800-FDA-1088; fax, 800-FDA-0178; or mail, MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857-9787; or online at http://www.fda.gov/medwatch/report.htm.
Reference details are available on the CDC site..