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Outbreak of Fusarium Keratitis in Soft Contact Lens Wearers in San Francisco
Maria D. Bernal, MD;
Nisha R. Acharya, MD;
Thomas M. Lietman, MD;
Erich C. Strauss, MD;
Stephen D. McLeod, MD;
David G. Hwang, MD
Arch Ophthalmol. 2006;124(7):1051-1053. Published online June 12, 2006 (doi:10.1001/archophthalmol.124.7.ecr60006).
We report a cluster of 4 cases of soft contact lens–associated Fusarium keratitis seen at the University of California, San Francisco (UCSF), during a 5-week span in early 2006 and compare this cluster with the number of previous cases of culture-positive Fusarium keratitis seen at UCSF during the prior 30 years. This cluster represents part of a larger outbreak of Fusarium keratitis currently under investigation by public health authorities in Singapore1 and the United States.2 As in these outbreaks under investigation, soft contact lens wear and use of ReNu with MoistureLoc or ReNu MultiPlus (Bausch & Lomb, Rochester, NY) contact lens solution was a common feature of these cases.
Report of Cases
Case 1. A 19-year-old, previously healthy woman was referred in February 2006 for presumed herpes simplex keratouveitis unresponsive to medical therapy. She wore daily-wear soft contact lenses and exclusively used ReNu with MoistureLoc contact lens solution. She was initially seen by her ophthalmologist with complaints of redness, irritation, and foreign body sensation in her left eye that had failed to respond to 1 week of broad-spectrum antibiotic drops prescribed by her optometrist. A presumptive clinical diagnosis of herpes simplex keratouveitis was made, and oral valacyclovir hydrochloride, topical 1% prednisolone acetate, and later oral prednisone were prescribed for worsening keratitis. She worsened over 4 weeks and was referred to the Francis I. Proctor Foundation at UCSF.
Visual acuity at initial examination was hand motions OS. A severe, multifocal, infiltrative stromal keratitis with a 1-mm hypopyon was noted in the left eye. The central and peripheral left cornea was studded with numerous fluffy, 0.2-mm, white infiltrates at all depths of the stroma, accompanied by a dense 3-mm infiltrate in the deep stroma paracentrally. No corneal thinning was noted. Giemsa stain of a corneal scraping showed branching, septated hyphae (Figure 1). Fungal keratitis was diagnosed, and a regimen of topical 5% natamycin, topical 0.15% amphotericin B, and oral itraconazole was started. In addition, the oral prednisone and valacyclovir administration were stopped; the prednisolone, rapidly tapered; and the antibiotic drops, continued.
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Figure 1. Corneal scraping from the patient, showing septated hyphae consistent with Fusarium.
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On identification of the fungal pathogen as being Fusarium, itraconazole administration was stopped and oral voriconazole administration begun. However, a fulminant course of worsening suppuration ensued (Figure 2), and 5 days after initial examination at UCSF, a limbus-to-limbus descemetocele accompanied by multiple small perforations (Figure 3) was noted. An emergency tectonic corneal transplantation was performed, and at the time of surgery, a dense, yellowish membrane filling the anterior chamber was excised. Fusarium was noted on histopathological examination and culture of both the membrane and the cornea, despite the antifungal treatment during the preceding 6 days.
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Figure 2. Severe Fusarium keratitis in a soft contact lens wearer 4 days after referral for presumed herpes simplex keratouveitis.
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Figure 3. Descemetocele occurring 5 days after initial examination at University of California, San Francisco, necessitating emergent penetrating keratoplasty.
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Postoperatively, 1% voriconazole drops were substituted for the natamycin and amphotericin B. Despite the use of topical 1% cyclosporine, graft rejection occurred 3 weeks after surgery. As of 7 weeks postoperatively, visual acuity was counting fingers at 2 ft and the graft remained free of signs of recurrent infection.
Case Series. From February 23, 2006, to March 30, 2006, 4 cases of culture-proven Fusarium keratitis were seen at the Francis I. Proctor Foundation and the Cornea Service of the Department of Ophthalmology at UCSF. All patients used soft contact lenses on a daily-wear basis.
Three of the 4 cases occurred in young (ages 19, 21, and 24 years), otherwise healthy female soft contact lens wearers with no other risk factors for fungal keratitis. All 3 of these patients exclusively used ReNu with MoistureLoc contact lens solution that had been purchased in various locations and at various times in the San Francisco Bay Area. The lot numbers and expiration dates were noted to be different for each of these 3 bottles.
The fourth case occurred in a 56-year-old female soft contact lens wearer undergoing CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) for non-Hodgkin lymphoma. This patient generally used COMPLETE Moisture Plus No Rub contact lens solution (Advanced Medical Optics, Santa Ana, Calif), but on 1 occasion 2 weeks prior to initial examination, she had also used ReNu MultiPlus, which she kept with her travel supplies.
None of the patients had clinical features that led the examining ophthalmologist to suspect the diagnosis of filamentous fungal keratitis. Two of the cases were presumed to be herpetic keratitis, and the other 2 were presumed to be bacterial keratitis. In 3 of the 4 cases, referral to UCSF was made within 5 days of initial examination, and all 3 of these cases did well, with improvement in best-corrected visual acuity to 20/40 or better after a course of topical antifungal therapy, with or without oral antifungal agents. In 1 of the 4 cases, described earlier, a 4-week delay between initial symptoms and diagnosis occurred, during which the patient was treated with oral and topical corticosteroids, and this patient required corneal grafting for severe keratitis with perforation.
Retrospective review of prior Fusarium keratitis cases seen at our institution disclosed only 8 cases during the previous 30 years (1976-2005). Only 2 of these cases occurred in contact lens wearers.
Comment
This cluster of cases appears to be part of a larger outbreak reported in February 2006 by the Singapore Health Ministry and in April 2006 by the Centers for Disease Control and Prevention (CDC) in the United States.1-2 At our institution, which is located in a temperate climate, Fusarium is an exceptionally uncommon cause of contact lens–associated keratitis, having accounted for only 2 such cases in the 30 years prior to the current episode.
Although the cause of the current outbreak has not yet been identified and is the subject of an ongoing epidemiological investigation by the CDC and other public health authorities, the use of Bausch & Lomb ReNu contact lens solution, and ReNu with MoistureLoc in particular, appears to be a common feature of these cases. In our series, ReNu with MoistureLoc was used exclusively by all 3 patients with no other risk factors for fungal keratitis. The fourth patient, who was immunocompromised because of recent chemotherapy, used at least 2 different contact lens solutions, including Bausch & Lomb ReNu MultiPlus solution. Of the 30 analyzed Fusarium cases reported by the CDC in April 2006, 28 were contact lens wearers.2 Of the 26 of those who recalled using a particular contact lens solution, all identified use of ReNu or a generic contact lens solution manufactured by Bausch & Lomb. Shortly after the CDC report appeared, Bausch & Lomb voluntarily withdrew ReNu with MoistureLoc contact lens solutions from the United States. In February 2006, a cluster of Fusarium cases in contact lens wearers was reported by the Singapore Health Ministry,1 and a strong association with ReNu with MoistureLoc use was noted. This report also led to the withdrawal of ReNu with MoistureLoc contact lens solution from the Singapore and Hong Kong markets.
In a May 5, 2006, press release,3 the CDC reported an update on its ongoing investigation. Of the 58 confirmed cases of Fusarium keratitis for which data collection had been completed, 56 reported using contact lenses. Of these contact lens–associated cases, 32 reported using Bausch & Lomb ReNu with MoistureLoc, 15 reported using Bausch & Lomb ReNu MultiPlus, 7 reported using an unspecified Bausch & Lomb ReNu product, 3 reported using a contact lens solution manufactured by Advanced Medical Optics, and 3 reported using a contact lens solution from Alcon Laboratories (Fort Worth, Tex) (some patients in this report used more than 1 contact lens solution). The CDC noted that the market share of ReNu MultiPlus was 5 times higher than that of ReNu with MoistureLoc, yet the majority of the analyzed Fusarium cases to date involved the use of ReNu with MoistureLoc.
Until this report, it has not been established whether the recent case reports represent a true increase in the incidence of Fusarium keratitis.2 Fusarium is not an uncommon cause of keratitis in tropical and subtropical climates, including those of southeast Asia and south Florida. Up to 35% of microbial keratitis cases reported from south Florida are attributable to fungal pathogens, compared with 1% from New York.4-5 There are relatively few reports of Fusarium keratitis in soft contact lens wearers,6 and the exact incidence of Fusarium keratitis in soft contact lens wearers is unknown. Our report strongly suggests that the current cluster represents an unusual spike over the background incidence of Fusarium keratitis seen during the prior 30 years at our institution. We believe that referral bias and reporting bias are unlikely to account for the increased number of cases seen, since all 4 cases came from established referral sources prior to the public announcement of Fusarium keratitis cases by the CDC.
We, other laboratories, and the CDC are currently investigating the fungicidal properties of the contact lens solutions used by these patients and the genotype characteristics of the Fusarium isolates of these cases in an effort to determine the underlying cause of the current apparent outbreak and whether the Fusarium species from these cases originate from a common strain.
Our case series also emphasizes the importance of corneal cultures in assisting with early diagnosis of microbial keratitis and the poor outcome of Fusarium keratitis when prolonged corticosteroid treatment is administered and appropriate antifungal treatment is delayed.
AUTHOR INFORMATION
Correspondence: Dr Hwang, Cornea Service, Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, K-301, San Francisco, CA 94143-0730 (david.hwang{at}ucsf.edu).
Published Online: June 12, 2006 (doi:10.1001/archophthalmol.124.7.ecr60006).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by unrestricted grants from Research to Prevent Blindness and That Man May See.
Author Contributions: Drs Bernal and Hwang contributed equally to this report.
Acknowledgment: We thank Vicky Cevallos, BS, and Cathy Donnellan, BS, for technical assistance with microbiology studies.
REFERENCES
1. Singapore Ministry of Health. Increasing incidence of contact lens related fungal corneal infections (update 3). February 21, 2006. http://www.moh.gov.sg/corp/about/newsroom/pressreleases/details.do?id=36077601. Accessed April 20, 2006.
2. Fusarium keratitis—multiple states, 2006. MMWR Morb Mortal Wkly Rep. 2006;55:400-401.
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3. Centers for Disease Control. Fusarium keratitis update. May 5, 2006. http://www.cdc.gov/od/oc/media/pressrel/r060505.htm. Accessed May 5, 2006.4. Liesegang TJ, Forster RK. Spectrum of microbial keratitis in south Florida. Am J Ophthalmol. 1980;90:38-47.
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5. Asbell P, Stenson S. Ulcerative keratitis: survey of 30 years' laboratory experience. Arch Ophthalmol. 1982;100:77-80.
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6. Foroozan R, Eagle RC Jr, Cohen EJ. Fungal keratitis in a soft contact lens wearer. CLAO J. 2000;26:166-168.
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SECTION EDITOR: W. RICHARD GREEN, MD
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