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Background: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data., Methods: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis., Results: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported., Conclusion: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Fusarium keratitis is a severe infection of the anterior eye, frequently leading to keratoplasty or surgical removal of the affected eye. A major risk factor for infection is the use of contact lenses. Inadequate hygiene precautions and mold-growth permissive storage fluids are important risk factors for fungal keratitis. The aim of this study was to comparatively analyze contact lens storage fluids disinfection efficacy against Fusarium species., Methods: Eleven commercially available storage fluids were tested. The storage fluids were classified according to their active ingredients myristamidopropyldimethylamine (Aldox), polyhexanide and hydrogen peroxide. Efficacy was tested against isolates belonging to the Fusarium solani and Fusarium oxysporum species complexes as the most common agents of mould keratitis. Tests were carried out based on DIN EN ISO 14729., Results: All Aldox and hydrogen peroxide (H 2 O 2 ) based fluids were effective against Fusarium spp., while the majority of polyhexanide based storage fluids showed only limited or no antifungal effects. Efficacy of polyhexanide could be restored by the addition of the pH-regulating agent tromethamine - an additive component in one commercially available product., Conclusions: In summary, the use of Aldox- or hydrogen peroxide-based storage fluids may reduce the risk of Fusarium keratitis, while polyhexanide-based agents largely lack efficacy against Fusarium., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: Sight-threatening infections can be caused by pathogenic micro-organisms colonising the cornea, leading to microbial keratitis (MK). These micro-organisms can be introduced to the eye via improper contact lens use and care. MK can also result from ineffective contact lens care solutions (CLCs), even if the patient is following best practice guidelines. Therefore, it is critical to understand the differences between the effectiveness of popular CLCs on the global market., Methods and Analysis: Following the International Standards Organisation standards 14 729 and 18259, bacteria ( Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus ), fungi ( Candida albicans, Fusarium strains) and Acanthamoeba strains were inoculated into each CLC with and without contact lenses, and held for the manufacturer's stated disinfection time. Plate counts were conducted to determine the number of surviving micro-organisms., Results: All CLCs examined met the primary log reduction criteria during stand-alone testing for Pseudomonas, Staphylococcus, Candida and Fusarium . renu Multiplus, All Clean Soft, and Kombilösung Super did not meet the primary criteria when challenged with Serratia . Only OPTI-FREE Express exceeded 4 log reduction for both strains of Acanthamoeba tested. We noted a substantial reduction in disinfection efficacy when CLCs were challenged with Fusarium in the presence of lenses and cases versus stand-alone testing. OPTI-FREE Express demonstrated significantly less net log reduction loss than the other four CLCs tested., Conclusion: Of the popular CLCs on the global market, the product which relies on dual biocides polyquaternium-1 and myristamidopropyl dimethylamine demonstrated the highest disinfection efficacy in microbial disinfection challenges in the absence and presence of contact lenses., Competing Interests: Competing interests: All authors are/were employees of Alcon Research., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome., Methods: Data from 173 cases reported in the German FK registry until August 2019 were evaluated regarding CL behavior, other ophthalmological and general risk factors, age, sex, identified pathogens, conservative and surgical therapy, visual acuity, and findings at admission and follow-up., Results: One hundred seventy-four eyes from 173 patients between 2000 and 2019 were included [64.4% women, median age 54 (39; 72) years]; 49.7% wore CL, of which 81.3% were soft CL, and 50.3% had no history of contact lens use (NCL). CL users were significantly more often women and otherwise healthy (CL: 80.2% vs. NCL: 48.9%; P < 0.0001). The spectrum of pathogens among CL users showed a significantly higher proportion of infections with filamentous pathogens, in particular Fusarium sp. (total filament: CL 69.8% vs. NCL 27.3%; P = 0.0001; Fusarium sp.: CL 50.0% vs. NCL 14.8%; P < 0.0001). Overall, 54.6% required keratoplasty and 8.6% enucleation., Conclusions: CLS are the most important risk factor for FK in Germany. With CLs, typically, the infection is caused by molds, and patients are comparably younger and otherwise healthy. Often, extensive surgery is needed. To evaluate changes in the pathogen and resistance spectrum and to further monitor possible CL-related risk factors, a consistent collection of data remains paramount., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study presents a device for efficient, low-cost and eye-friendly overnight disinfection of contact lenses by visible violet light as an alternative to disinfection with biocide-containing solutions. Bacterial solutions with one Pseudomonas and one Staphylococcus strain each were irradiated for up to 8 h in commercial transparent contact lens cases by the presented light-emitting diode (LED) device. Samples were taken at different intervals and distributed on agar plates. The surviving bacteria were determined by counting of colony-forming units and compared to the specific requirements of the stand-alone test for contact lens disinfection of the hygiene standard ISO 14729. The concentration of both microorganisms was reduced by three orders of magnitude after less than 4 h of irradiation. The LED current and intensity have not yet been at maximum and could be further increased if necessary for other microorganisms. The presented device fulfils the requirement of the stand-alone test of the contact lens hygienic standard ISO 14729 for the tested Pseudomonas and Staphylococcus strains. According to literature data, the inactivation of Serratia marcescens, Candida albicans and Fusarium solani seems also possible, but may require increased LED current and intensity.

Fusarium keratitis is a destructive eye infection that is difficult to treat and results in poor outcome. In tropical and subtropical areas, the infection is relatively common and associated with trauma or chronic eye diseases. However, in recent years, an increased incidence has been reported in temperate climate regions. At the German National Reference Center, we have observed a steady increase in case numbers since 2014. Here, we present the first German case series of eye infections with Fusarium species. We identified Fusarium isolates from the eye or eye-related material from 22 patients in 2014 and 2015. Thirteen isolates belonged to the Fusarium solani species complex (FSSC), 6 isolates belonged to the Fusarium oxysporum species complex (FOSC), and three isolates belonged to the Fusarium fujikuroi species complex (FFSC). FSSC was isolated in 13 of 15 (85%) definite infections and FOSC in 3 of 4 (75%) definite contaminations. Furthermore, diagnosis from contact lens swabs or a culture of contact lens solution turned out to be highly unreliable. FSSC isolates differed from FOSC and FFSC by a distinctly higher MIC for terbinafine. Outcome was often adverse, with 10 patients requiring keratoplasty or enucleation. The use of natamycin as the most effective agent against keratitis caused by filamentous fungi was rare in Germany, possibly due to restricted availability. Keratitis caused by Fusarium spp. (usually FSSC) appears to be a relevant clinical problem in Germany, with the use of contact lenses as the predominant risk factor. Its outcome is often adverse., (Copyright © 2017 American Society for Microbiology.)

Purposes: The purposes of this study were to determine whether the contact lens solution RevitaLens Ocutec (containing the antimicrobial agents alexidine and polyquaternium-1) would inhibit Fusarium organisms when heated in ReNu plastic bottles; whether alexidine would inhibit Fusarium organisms when heated in non-ReNu plastic bottles; and whether an alexidine-neutralizing compound leaches from heated ReNu bottles., Methods: RevitaLens and an alexidine solution (0.00045%), previously stored in ReNu bottles at room temperature (RT) and 56°C, were incubated with 7 different Fusarium organisms. The alexidine solution was similarly stored in seven non-ReNu plastic bottles and incubated with these same organisms. To determine if an alexidine-neutralizing compound might be leaching from heated ReNu bottles, phosphate-buffered saline (PBS) was incubated at RT and 56°C in ReNu bottles, combined with alexidine, and then tested for anti-Fusarium capability., Results: After being heated in ReNu bottles, RevitaLens retained its anti-Fusarium capability, whereas the alexidine solution did not. The alexidine solution heated in seven non-ReNu plastic bottles retained its anti-Fusarium capability. The alexidine solution retained its anti-Fusarium capability when incubated with a PBS solution that had been heated in ReNu bottles, indicating, microbiologically, that an alexidine-neutralizing compound did not leach from the heated ReNu bottle., Conclusions: Alexidine uniquely fails to inhibit Fusarium organisms when heated in a plastic ReNu bottle, but not in seven other plastic bottles, whereas the anti-Fusarium capability of RevitaLens (containing the antimicrobial agents alexidine and polyquaternium-1) is unaffected by heating in a ReNu bottle. There does not seem to be an alexidine-neutralizing compound leaching from heated ReNu bottles. An interaction between alexidine and its heated ReNu bottle may have been a critical factor in the worldwide ReNu with MoistureLoc-related Fusarium keratitis event of 2004 to 2006.

The incidence of Acanthamoeba and Fusarium species has increased in contact lens-related infectious keratitis. They share several environments and cases of co-infection have been reported. The interaction between the amoebae and other microorganisms may result in significant changes for both, like increased virulence in mammalian hosts. In this study, we evaluated the interaction of three Acanthamoeba castellanii strains with Fusarium conidia and the possible implications on keratitis. F. conidia were internalized by A. castellanii strains and were able to germinate inside the amoebae. The co-culture with the live amoebae, as well as the amoebal culture supernatant and lysate, increased the fungal growth significantly. Moreover, live F. solani and its culture supernatant enhanced the survival of amoebae, but in a different way in each amoebal strain. The encystment of the A. castellanii strain re-isolated from rat lung was increased by the fungus. These results show that A. castellanii and F. solani interaction may have an important influence on survival of both, and specially indicate a possible effect on virulence characteristics of these microorganisms. These data suggest that the A. castellanii-F. solani interaction may cause severe impacts on keratitis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Recent work has shown that Fusarium species and genotypes most commonly associated with human infections, particularly of the cornea (mycotic keratitis), are the same as those most commonly isolated from plumbing systems. The species most dominant in plumbing biofilms is Fusarium keratoplasticum, a cosmopolitan fungus known almost exclusively from animal infections and biofilms. To better understand its diversity and population dynamics, we developed and utilized a nine-locus sequence-based typing system to make inferences about clonality, recombination, population structure, species boundaries and hybridization., Results: High levels of genetic diversity and evidence for recombination and clonality were detected among 75 clinical and 156 environmental isolates of Fusarium keratoplasticum. The multilocus sequence typing system (MLST) resolved 111 unique nine-locus sequence types (STs). The single locus bifactorial determinants of mating compatibility (mating types MAT1-1 and MAT1-2), were found in a ratio of 70:30. All but one of the 49 isolates of the most common ST (FSSC 2d-2) came from human infections, mostly of the cornea, and from biofilms associated with contact lenses and plumbing surfaces. Significant levels of phylogenetic incongruence were found among loci. Putative clonal relationships among genotypes were estimated, showing a mixture of large clonal complexes and unrelated singletons. Discordance between the nuclear ribosomal rRNA and other gene genealogies is consistent with introgression of ribosomal RNA alleles of phylogenetic species FSSC 9 into F. keratoplasticum. No significant population subdivision based on clinical versus non-clinical sources was found., Conclusions: Incongruent phylogenetic trees and the presence of both mating types within otherwise identical STs were observed, providing evidence for sexuality in F. keratoplasticum. Cryptic speciation suggested in a published three-locus MLST system was not supported with the addition of new loci, but evidence of introgression of ribosomal RNA genes from another strongly supported phylogenetic species (FSSC 9), also known from plumbing systems and human infections, was detected in two isolates. Overall, F. keratoplasticum is a diverse and geographically unstructured species with a mixed clonal and recombinant life history.

Objective: ReNu with MoistureLoc (ReNuML), containing the antimicrobial agent alexidine 0.00045%, was associated with the Fusarium keratitis epidemic of 2004 to 2006. Although a single-point source contamination was ruled out, only Fusarium organisms were reported during the outbreak. This study investigated whether the reported loss of antimicrobial effectiveness toward Fusarium of ReNuML after exposure to heat in high-density polyethylene (HDPE) plastic containers could also be demonstrated with other common fungal and bacterial agents of keratitis., Methods: A buffered solution of alexidine 0.00045% was incubated in glass and ReNu HDPE plastic containers at room temperature (RT) and 56°C for 4 weeks, serially diluted, and tested for its ability to inhibit the growth of 20 bacterial isolates, 12 non-Fusarium fungal isolates, and 7 Fusarium isolates originally involved in the keratitis epidemic., Results: A statistically significant loss of antimicrobial capability was seen with all fungi, all gram-positive bacteria, and all isolates of Klebsiella when alexidine 0.00045% was incubated at 56°C in ReNu HDPE containers compared with RT or glass incubation (P≤0.0001)., Conclusions: Heating of an alexidine solution in ReNu HDPE plastic (but not glass) containers results in the same loss of anti-Fusarium activity as reported when testing the original ReNuML solution. This loss of inhibitory activity is not specific to Fusarium and occurs with other fungi and bacteria that cause keratitis. The reasons for the lack of reports of bacterial and/or non-Fusarium fungal keratitis during the original Fusarium keratitis epidemic remain unclear at this time.

Objective: To demonstrate the effects of time, temperature, and container properties on the ability of ReNu with MoistureLoc (ReNuML; contains the antimicrobial agent alexidine) to inhibit growth of Fusarium species., Methods: ReNu with MoistureLoc was stored in its Bausch & Lomb (Rochester, New York) plastic or similarly sized glass containers for 1 and 4 weeks at room temperature, 42°C, and 56°C, and then tested for its ability to inhibit growth of 7 Fusarium isolates., Results: ReNu with MoistureLoc stored in glass containers for 1 or 4 weeks at all 3 temperatures demonstrated no significant fungistatic deterioration. However, ReNuML stored at 56°C in its Bausch & Lomb plastic container demonstrated a statistically significant fungistatic deterioration compared with room temperature storage in its original plastic container or with glass container storage at any temperature., Conclusion: When exposed to elevated storage temperature, it appears that an interaction between ReNuML and its Bausch & Lomb plastic container adversely affects the fungistatic properties of ReNuML, which could have contributed to the Fusarium keratitis epidemic of 2004 through 2006.

Objective: Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population., Design: Retrospective, multicenter case series., Participants: Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007., Methods: Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research., Main Outcome Measures: Quarterly number of fungal keratitis cases and fungal species., Results: We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P < 0.0001)., Conclusions: The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the public health implications of 2 recent outbreaks of atypical contact lens-related infectious keratitis., Design: Perspective based on the literature and authors' experience., Results: The contact lens-related Fusarium and Acanthamoeba keratitis outbreaks were each detected by dramatic rises seen in tertiary care centers in Singapore and the United States, respectively. Case-control studies of both outbreaks were able to identify a strong association with the use of different contact lens disinfection solutions. Their respective recalls resulted in a steep decline of Fusarium keratitis, but not of Acanthamoeba keratitis. Early investigations into each solution association implicated components not directly related to their primary disinfectant, but the true pathogenesis remains unknown. However, the number of Acanthamoeba cases individually attributed to each of almost all available disinfection systems exceeds the previously understood total United States incidence, suggesting other risk factors. Current standards do not require demonstration of anti-acanthamoebal activity. Yet, despite the inclusion of Fusarium in mandatory testing for solutions, current premarket testing was not predictive of the outbreak., Conclusions: The 2 recent outbreaks of atypical contact lens-related keratitis have reinforced the value of tertiary care eye care centers in detecting early rises in rare infections and the power of adaptable, well-designed epidemiologic investigations. Although Fusarium keratitis has declined significantly with the recall of Renu with MoistureLoc (Bausch & Lomb Inc.), the persistence of Acanthamoeba keratitis demands fundamental changes in contact lens hygiene practices, inclusion of Acanthamoeba as a test organism, and contact lens disinfectant test regimens for all contact lens-related pathogens that are verifiably reflective of end user contact lens wear complications., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To examine seven cases of contact lens-related Fusarium keratitis that resulted in therapeutic penetrating keratoplasty, to investigate which factors were associated with favorable versus poor graft outcome in this population., Methods: Seven patients who underwent corneal transplant after contact lens-related, culture-proven Fusarium keratitis were identified through a retrospective chart review. The cases occurred between September 2005 and January 2006 at the University of Medicine and Dentistry of New Jersey and Wills Eye Hospital. All seven patients had used Bausch and Lomb's ReNu with MoistureLoc. The outcomes studied were graft status, infection recurrence, and 6-month postoperative visual acuity., Results: The rejection rate was 57.1% and the recurrence rate was 28.6% in this study. No eyes were lost to fungal endophthalmitis. In this population, larger ulcer size and a greater total number of medical agents used before and after penetrating keratoplasty were significantly associated with poor outcomes, namely graft rejection and poor visual acuity. In addition, it was noted that the patients who suffered recurrence of infection had both a larger median graft size and a longer median duration of postoperative antifungal use although these results did not reach statistical significance., Conclusions: Larger ulcer size, larger graft size, a greater number of medical agents used, and a longer duration of postoperative antifungal therapy may be useful parameters in predicting surgical outcomes in patients with fungal keratitis. Further research is needed to validate our results and to elucidate the mechanisms behind graft rejection in the setting of fungal keratitis.

Purpose: Fusarium solani and F. oxysporum were the causative organisms of the 2005/2006 outbreak of contact lens-associated fungal keratitis in the United States. The present study was an investigation of the ability of F. oxysporum grown as a biofilm on silicone hydrogel contact lenses to induce keratitis., Methods: A clinical isolate of F. oxysporum was grown as a biofilm on lotrafilcon A contact lenses, and a 2-mm diameter punch was placed on the abraded corneal epithelium of either untreated or cyclophosphamide-treated C57BL/6 mice or of IL-1R1(-/-), MyD88(-/-), TLR2(-/-), or TLR4(-/-) mice. After 2 hours, the lens was removed, and corneal opacification, colony forming units (CFUs), and histopathology were evaluated., Results: C57BL/6 mice developed severe corneal opacification within 24 hours and resolved after four days. In contrast, corneal opacification progressed in cyclophosphamide-treated mice, and was associated with unimpaired fungal growth in the cornea, and with hyphae penetrating into the anterior chamber. The phenotype of MyD88(-/-) and IL-1R(-/-) mice was similar to that of cyclophosphamide-treated animals, with significantly impaired cellular infiltration and fungal clearance. Although TLR4(-/-) mice developed a cellular infiltrate and corneal opacification similar to C57BL/6 mice, the CFU count was significantly and consistently higher., Conclusions: Fusarium grown as a biofilm on silicone hydrogel contact lenses can induce keratitis on injured corneas, with disease severity and fungal killing dependent on the innate immune response, including IL-1R1, MyD88, and TLR4.

Objective: To investigate the effect of storage temperature on the ability of contact lens solutions to inhibit growth of Fusarium species. A 2006 Food and Drug Administration inspection of Bausch & Lomb's Greenville, South Carolina, manufacturing site indicated that Bausch & Lomb failed to regulate storage and transport temperatures of their products., Methods: Six contact lens solutions were studied: ReNu with MoistureLoc, ReNu MultiPlus, COMPLETE Moistureplus, AQuify, Clear Care, and OPTI-FREE RepleniSH. Two bottles of each solution were separately stored at room temperature and 60 degrees C for 4 weeks, serially diluted, and then tested for their ability to inhibit growth of 11 Fusarium isolates (7 of which were associated with the keratitis epidemic)., Results: ReNu with MoistureLoc demonstrated the greatest decline in efficacy after 60 degrees C storage. Clear Care and ReNu MultiPlus performed the best. Regarding the keratitis epidemic isolates only, the ReNu with MoistureLoc bottle stored at room temperature allowed growth in 27 of 84 combinations vs 67 of 84 combinations with the 60 degrees C-stored bottle., Conclusions: When exposed to prolonged temperature elevation, ReNu with MoistureLoc loses its in vitro fungistatic activity to a much greater extent than other products. Improper temperature control of ReNu with MoistureLoc may have contributed to the Fusarium keratitis epidemic of 2004-2006.

Background: In Singapore, an outbreak of fungal keratitis caused by members of the Fusarium solani species complex (FSSC) was identified in March 2005 to May 2006 involving 66 patients. Epidemiological investigations have indicated that improper contact lens wear and the use of specific contact lens solutions were risk factors., Methods: We assessed the genetic diversity of the isolates using AFLP, Rep-PCR, and ERIC-PCR and compared the usefulness of these typing schemes to characterize the isolates., Results: AFLP was the most discriminative typing scheme and appears to group FSSC from eye infections and from other infections differently., Conclusion: There was a high genomic heterogeneity among the isolates confirming that this was not a point source outbreak.

Purpose: A 2006 US Food and Drug Administration (FDA) inspection of Bausch & Lomb's (B&L's) Greenville, South Carolina, manufacturing site indicated that B&L failed to regulate storage and transport temperatures of their products. The present study investigated the effect of storage temperature on the ability of contact lens solutions to inhibit growth of Fusarium species., Methods: SIX CONTACT LENS SOLUTIONS WERE STUDIED: ReNu with MoistureLoc (ReNu ML), ReNu MultiPlus, Complete Moistureplus, AQuify, Clear Care, and OPTI-FREE RepleniSH. Two bottles of each solution were separately stored at room temperature and 60 degrees C for 4 weeks, serially diluted, then tested for their ability to inhibit growth of 11 Fusarium isolates (7 of which were associated with the keratitis epidemic)., Results: ReNu ML demonstrated the greatest decline in efficacy after 60 degrees C storage. Clear Care and ReNu MultiPlus performed the best. Regarding the keratitis epidemic isolates only, the ReNu ML bottle stored at room temperature allowed growth in 27 of 84 combinations vs 67 of 84 combinations with the 60 degrees C stored bottle., Conclusions: When exposed to prolonged temperature elevation, ReNu ML loses its in vitro fungistatic activity to a much greater extent than other products. Improper temperature control of ReNu ML may have contributed to the Fusarium keratitis epidemic of 2004-2006.

Purpose: To report the clinical features and management outcomes of a cluster of Fusarium keratitis in patients that used the Bausch & Lomb ReNu MostureLoc contact lens solution., Methods: Retrospective case series., Results: In a 1-year period starting from June 2005, we treated 12 patients with unilateral Fusarium keratitis in our tertiary care center. All patients were contact lens users that used ReNu MostureLoc contact lens solution and had no other specific predisposing conditions. Microbiological examination yielded growth of Fusarium spp. in 7 patients from corneal scrapings at presentation and from 3 patients in subsequent corneal specimens. For 2 other patients, fungi were not detected from corneal scrapings, but Fusarium spp. were isolated from their contact lenses. The infections were treated with topical natamycin and amphotericin B eye drops and with systemic itraconazole in 8 patients. The infection resolved with medical treatment in 8 eyes, a conjunctival flap in 1 eye, and a therapeutic corneal graft in 1 eye. Two eyes required tectonic corneal grafts for perforation. Two of the 3 corneal grafts failed because of graft rejection. Final visual acuities ranged from count fingers to 1.0., Conclusions: This cluster of Fusarium keratitis seems to be related to the use of the ReNu MoistureLoc contact lens solution. The cure rate with medical therapy was 66%. However, corneal scarring limited visual recovery. This episode highlights the need for clinical vigilance when dealing with corneal infiltrates in contact lens users.

Purpose: To report an outbreak of Fusarium keratitis in contact lens (CL) wearers in the northeastern United States., Methods: Over a 41-month period, all cases with culture-proven corneal ulceration secondary to Fusarium at 2 tertiary care eye centers were identified through the microbiology departments of each institution, and a retrospective review of charts was performed. Statistical analyses were performed to evaluate a possible association of Fusarium keratitis with specific CL and CL solution brands., Results: Fifteen cases of Fusarium keratitis were reported at the 2 tertiary centers between July 2005 and May 2006 (16.4 cases/yr) compared with 6 cases over the previous 30 months from January 2003 to June 2005 (2.4 cases/yr). All 15 of the more recent cases were CL users, and none had a history of trauma. All 15 patients claimed use of ReNu brand contact lens solution when they developed keratitis. Twelve (80.0%) of 15 patients were Acuvue soft contact lens users. Ten (66.7%) of 15 patients used tap water to rinse their contact lens cases. Six (40.0%) of 15 cases have thus far required corneal transplantation., Conclusions: The incidence of corneal ulceration secondary to Fusarium has increased sevenfold over the reported 11-month period at 2 tertiary eye care centers in the northeastern United States compared with the previous 30 months. There seems to be an association between the recent outbreak of Fusarium keratitis among CL users and the use of ReNu contact lens solution. Medical treatment of Fusarium keratitis may be ineffective, and emergent penetrating keratoplasty (PKP) may be required in some patients. CL users and their physicians should reconsider the risks of CL use and discuss proper lens care techniques.

In 2005 and 2006, outbreaks of Fusarium keratitis associated with soft contact lens use occurred in multiple U.S. states and Puerto Rico. A case-control study conducted by the Centers for Disease Control and Prevention (CDC) showed a significant association between infections and the use of one particular brand of lens solution. To characterize the full spectrum of the causal agents involved and their potential sources, partial DNA sequences from three loci (RPB2, EF-1alpha, and nuclear ribosomal rRNA) totaling 3.48 kb were obtained from 91 corneal and 100 isolates from the patient's environment (e.g., contact lens and lens cases). We also sequenced a 1.8-kb region encoding the RNA polymerase II second largest subunit (RPB2) from 126 additional pathogenic isolates to better understand how the keratitis outbreak isolates fit within the full phylogenetic spectrum of clinically important fusaria. These analyses resulted in the most robust phylogenetic framework for Fusarium to date. In addition, RPB2 nucleotide variation within a 72-isolate panel was used to design 34 allele-specific probes to identify representatives of all medically important species complexes and 10 of the most important human pathogenic Fusarium in a single-well diagnostic assay, using flow cytometry and fluorescent microsphere technology. The multilocus data revealed that one haplotype from each of the three most common species comprised 55% of CDC's corneal and environmental isolates and that the corneal isolates comprised 29 haplotypes distributed among 16 species. The high degree of phylogenetic diversity represented among the corneal isolates is consistent with multiple sources of contamination.

Purpose: To report 5 cases of fungal keratitis associated with contact lens wear that resolved or significantly improved without antifungal therapy., Methods: Observational case report of 5 patients with a history of contact lens wear who presented with infectious keratitis. Two patients had growth of fungal species on corneal microbiologic cultures, and of the remaining 3 patients, 2 showed fungal elements on confocal microscopy. All 5 patients exhibited growth of fungal species on contact lens microbiologic cultures. All patients received topical fluoroquinolone therapy as initial treatment., Results: In 3 cases, of whom 2 were treated with moxifloxacin 0.5%, the keratomycosis resolved completely on topical fluoroquinolone therapy. One case was switched to topical tobramycin 14 mg/mL and cefazolin 50 mg/mL with complete resolution of the infection. The final case showed marked initial improvement on fluoroquinolone therapy but was subsequently treated with natamycin 5%., Conclusions: Fungal keratitis associated with soft contact lens wear may occasionally present in a less aggressive form. Topical fluoroquinolone therapy may be an adjunct to the innate immune response in eradicating less fulminant keratomycosis.

Background: To characterize Fusarium isolates from recent cases of fungal keratitis in contact lens wearers, and to investigate fungal association with MoistureLoc solution., Methods: We studied six fungal isolates from recent cases of keratitis in New York State. The isolates were characterized by nucleotide sequencing and phylogenetic analyses of multiple genes, and then typed using minisatellite and microsatellite probes. Experimental fungal biofilm formation was tested by standard methods. MoistureLoc solutions were tested in biofouling studies for their efficacy in elimination of Fusarium contamination., Results: Fusarium solani--corneal ulcers (2 isolates), lens case (1 isolate), and F. oxysporum--corneal ulcer (1 isolate), eye (1 isolate), were recovered from five patients. An opened bottle of MoistureLoc solution provided by a patient also yielded F. solani. Two distinct genotypes of F. solani as well as of F. oxysporum were present in the isolated strains. Remarkably, F. solani strains from the lens case and lens solution in one instance were similar, based on phylogenetic analyses and molecular typing. The solution isolate of F. solani formed biofilm on contact lenses in control conditions, but not when co-incubated with MoistureLoc solution. Both freshly opened and 3-month old MoistureLoc solutions effectively killed F. solani and F. oxysporum, when fungal contamination was simulated under recommended lens treatment regimen (4-hr). However, simulation of inappropriate use (15-60 min) led to the recovery of less than 1% of original inoculum of F. solani or F. oxysporum., Conclusion: Temporary survival of F. solani and F. oxysporum in MoistureLoc suggested that improper lens cleaning regimen could be a possible contributing factor in recent infections.

Purpose: Recent reports of disproportionate outbreaks of microbial keratitis caused by Fusarium solani have led to the removal of the Bausch & Lomb multipurpose lens care solution ReNu With MoistureLoc ("MoistureLoc") from the global market. Previous studies have shown an increased risk of contact lens-related corneal infection in connection with overnight wear, noncompliant lens wearing and lens care behaviors, specific treatment regimens, and other patient-related and non-patient-related factors. The purpose of the laboratory evaluations reported in this article were to observe the effects of levels of simulated lens care noncompliance on the antimicrobial efficacy of multipurpose solutions following recent reports of F. solani keratitis., Methods: Two multipurpose contact lens care solutions, MoistureLoc and ReNu MultiPlus multipurpose solution ("ReNu MultiPlus"), were tested under conditions that attempted to simulate the possible effect of the noncompliant behaviors reported to Bausch & Lomb as part of the investigation into cases of Fusarium keratitis. Testing conditions included simulated multiple reuse of solutions and evaporation of solutions., Results: The biocidal efficacy of MoistureLoc and other tested solutions was reduced under conditions that simulated the possible impact of solution reuse. Further investigation of MoistureLoc and ReNu MultiPlus suggests that although efficacy with ReNu MultiPlus was maintained across a variety of noncompliant conditions, the MoistureLoc formula could be rendered less effective under certain conditions., Conclusions: Under conditions simulating the possible impact of noncompliance, the MoistureLoc solution showed reduced biocidal efficacy. In contrast, ReNu MultiPlus retained a higher level of biocidal activity under the same conditions.

Purpose: To determine the effectiveness of multipurpose contact lens solutions after incubation with lenses for one week., Methods: Five multipurpose solutions, three lots each, were preincubated with contact lenses for one week. The solutions were removed and one of three microbes was added to a final concentration of l x l0(6)/mL. The inoculated solutions were incubated for 4 and 6 hours; aliquots were then neutralized, serially diluted, and plated. Plate counts were used to determine the approximate number of organisms that were killed effectively by the contact lens solution., Results: Of the five solutions tested, only OPTI-FREE Express maintained full effectiveness after preincubation with lenses. The other solutions were effective only with Fusarium solani after the preincubation period., Conclusions: We propose that the active component was sufficiently reduced by absorption or inactivation during storage with contact lenses such that it was rendered effective only for F. solani and was no longer concentrated enough to be effective with the bacterial species.