Fusarium—A New Culprit in the Contact Lens Case

Commentary

Microbial keratitis is a vision-threatening infection of the cornea caused by different infectious agents including viruses, bacteria, fungi, and protozoa. Risk factors for infection with nonviral agents include trauma, contact lens wear, and chronic ocular surface disease. In the United States, the incidence of corneal ulceration is about 11 per 100 000 person-years,¹ and contact lens wear is the most important risk factor. In developing countries, such as those in South Asia, ocular trauma is the principle risk factor for infectious keratitis.^{2 - 3} Furthermore, the annual incidence of infectious keratitis in South Asia appears to be from 10 (113 per 100 000 persons)⁴ to 70 (799 per 100 000 persons)⁵ times greater than in the United States.

Bacterial infections are the principle cause of microbial keratitis in the United States, whereas fungal infections account for between 20% and 70% of all corneal ulcers in a number of developing countries in Africa⁶ and Asia.^{2 - 3 ,7} In South India,³ most fungal ulcers are filamentous, with 47% caused by Fusarium species and 25% caused by Aspergillus species.

Filamentous fungal keratitis is notoriously difficult to treat despite the use of topical and systemic antifungal agents but Fusarium keratitis is truly a therapeutic challenge. Many patients require adjuvant surgery ranging from recurrent corneal debridement to corneal transplantation but the visual outcome is often dismal. Few prospective studies have evaluated the effectiveness of different therapeutic approaches for fungal keratitis but ophthalmologists in developing countries have been warning for years of the “silent epidemic” of corneal blindness due to bacterial and fungal ulcers.⁸

During the first 4 months of 2006, both the Singapore Health Ministry and the US Centers for Disease Control and Prevention (CDC) reported outbreaks of fungal keratitis associated with contact lens wear.^{9 - 10} The initial CDC report specified 109 cases that were under investigation and a follow-up report in May 2006 detailed the medical history of the 58 confirmed cases.¹¹ Of these 58 cases, 56 were associated with contact lens wear and 54 reportedly had used a Bausch and Lomb contact lens solution, including 32 cases who specified using ReNu with MoistureLoc. These reports led to professional and public warnings about a possible association of the ReNu brand of contact lens solutions and fungal keratitis as well as a worldwide withdrawal of ReNu with MoistureLoc from the marketplace. In this issue of JAMA, Chang and colleagues¹² report that by the end of June 2006, the CDC had confirmed a total of 176 cases of Fusarium keratitis in 164 patients in 33 states, the majority of whom were wearing soft contact lenses and reportedly had been using ReNu with MoistureLoc.

Outbreaks of Fusarium keratitis related to contact lens wear in the San Francisco Bay Area, Southern Florida, and Singapore are described in detail in 3 recent studies, 2 of which were published recently in the Archives of Ophthalmology.^{13 - 14} Bernal and colleagues¹³ described the clinical presentation and course of 4 sequential patients with Fusarium keratitis presenting at the University of California, San Francisco, over a 5-week period during February and March of 2006. All 4 patients were contact lens wearers and had been using ReNu with MoistureLoc as part of their contact lens care regimen. To address the question of whether this short case series represents a true outbreak, the authors noted only 8 prior cases of Fusarium keratitis at their center over the previous 30 years. Alfonso and colleagues¹⁴ reported the clinical presentations and course of 34 cases of Fusarium keratitis among contact lens users presenting to the Bascom Palmer Eye Institute in Miami over a 2-year period from January 2004 to April 15, 2006. Of the 13 cases in which the type of contact lens solution was identified, 12 were Bausch and Lomb ReNu products. Contact lenses from 11 patients were available for culture and 7 grew Fusarium. Fungal keratitis has always represented a greater percentage of infectious keratitis cases in tropical areas such as South Florida than in temperate San Francisco. Nonetheless, fungal keratitis related to contact lens wear was rarely seen previously by this group, with published records of only 10 cases from 1969 to 1992.^{15 - 17}

In a third recent study, Khor and colleagues¹⁸ reported the clinical details of 66 cases of Fusarium keratitis identified in Singapore from March 2005 through May 2006, an epidemic that peaked in February 2006, the same month that sales of ReNu solutions were stopped in Singapore. Almost all of the patients (98.5%) wore soft contact lenses and 93.9% reported using the ReNu brand of multipurpose lens solution, including 42 patients (63.5%) who specifically reported using ReNu with MoistureLoc. Contact lens hygiene was considered suboptimal in more than 80% of the patients. Thirty-five of these 66 cases of Fusarium keratitis were identified at the Singapore National Eye Center, representing a marked increase in the incidence of Fusarium keratitis associated with contact lens wear from 2000 to 2004 when only 3 cases were identified at this same institution.

These studies together with the accumulating CDC data suggest a recent epidemic of Fusarium keratitis in contact lens wearers. Discussions and debates at professional meetings and on professional list servers suggest that this epidemic may be even larger than recognized by the CDC. The true size of this epidemic will only be known after all of the potential cases have been reported and rigorously followed-up by the CDC. Are Bausch and Lomb products a risk factor? Given the high penetration of these products in the marketplace, this issue deserves further study. In addition, given the relatively small percentage of contact lens wearers in the United States that use ReNu with MoistureLoc (estimated at 2.3 million of the 30 million contact lens wearers),^{10 - 11} this specific product is suspect.

However, the broader question that deserves further attention is whether multipurpose contact lens solutions, although more convenient to use, are less effective against fungi than lens care systems that use a separate disinfection solution, such as hydrogen peroxide. Even though ReNu with MoistureLoc has been implicated as the potential culprit in this epidemic, the article by the CDC reported that Fusarium has not been recovered from the factory, warehouse, solution filtrate, or in any unopened bottles of the product in question; the article also revealed the high-genetic diversity of the genotyped Fusarium specimens analyzed.¹² While not definitive, these findings suggest that intrinsic contamination of the contact lens solution does not appear to be the direct cause of the infections.

The current epidemic of Fusarium keratitis should lead to increased public and professional awareness about the preventive measures for and early clinical recognition of infectious keratitis. Preventive measures include proper storage, disinfection, and cleaning of contact lenses and their cases. Additional measures include avoiding overnight contact lens wear and the prompt removal of contact lenses at the onset of any ocular irritation. Unfortunately, few contact lens wearers take these precautions seriously. Perhaps the current epidemic will change some of this behavior. The benefit of early recognition is highlighted by the report by Alfonso et al¹⁴ in which patients with early initiation of antifungal therapy had more rapid resolution of their disease. Early signs and symptoms of infectious keratitis include redness, tearing, pain, light sensitivity, discharge, decreased vision, and a white corneal infiltrate. However, more specific signs of fungal keratitis, such as a corneal stromal infiltrate with “feathery edges,” satellite lesions, a ring infiltrate, a posterior endothelial plaque, or a waxing and waning hypopyon were absent in some of the recently reported cases.¹² Thus, early recognition depends critically on a high index of suspicion and appropriate diagnostic studies, including cytological staining and microbiological cultures of material from the involved site.

Topical ophthalmic corticosteroids, usually in combination with an antibacterial, are commonly prescribed by physicians for patients with complaints of acute red eyes, frequently by telephone and without a physical evaluation. However treatment of infectious keratitis with a corticosteroid in the absence of appropriate antimicrobial therapy is contraindicated.¹⁹ Despite this, about one fourth of the cases reported in the United States had received a topical corticosteroid prior to referral and initiation of antifungal therapy.^{13 - 14} Clinicians must immediately cease this potentially harmful practice. This is particularly important for the management of fungal keratitis, for which the most appropriate antimicrobial therapies have yet to be determined. There is a need for research in this area; however, it is most likely that any well-designed clinical trial on the treatment of fungal keratitis will be conducted outside of the United States in countries where patient recruitment can be more effectively achieved.

While the current epidemic of Fusarium keratitis in the United States is relatively small and will likely be limited, it has attracted the attention of the ocular infectious disease community. Hopefully, this interest will translate into future research studies and clinical recommendations that can benefit care in areas of the world where fungal keratitis is not a brief epidemic but a daily occurrence. Unfortunately, these are the same countries that can ill afford to meet the medical, social, and economic challenges posed by the blindness that Fusarium keratitis leaves in its wake.