MS NO: ICO201711 CLINICAL SCIENCE Update on Fungal Keratitis From 1999 to 2008 Elvin H. Yildiz, MD, Yasmine F. Abdalla, MD, Ahmed F. Elsahn, MD, Christopher J. Rapuano, MD, Kristin M. Hammersmith, MD, Peter R. Laibson, MD, and Elisabeth J. Cohen, MD Purpose: To report trends in fungal keratitis from a single institution between 1999 and 2008. Methods: Retrospective chart review of the patients presenting to the cornea service with fungal keratitis from April 1999 to December 2008. Results: Seventy-eight eyes of 76 patients were identified. The most common predisposing factors included contact lens use (35.9%), trauma (21.8%), and history of penetrating keratoplasty (15.4%). There was a significant increase in the rate of contact lens–related Fusarium infections over time, which peaked in 2005 and 2006 (P = 0.021). Almost 40% of fungal keratitis cases [11 of 28 eyes (39.3%)] were soft contact lens–related Fusarium infections in 2005 and 2006, and this decreased to less than 10% [2 of 25 eyes (8%)] in 2007 and 2008. The odds of having a contact lens–related Fusarium infection in 2005–2006 compared with 2007–2008 was 4.40 (95% confidence interval of 0.60–32.50) (P = 0.178). Despite the decrease in contact lens–related Fusarium infections, the number of fungal infections remained elevated in 2007 (10 eyes) and 2008 (14 eyes), including contact lens–related infections (3 in 2007 and 6 in 2008). Conclusions: A definite increase in the number of fungal keratitis cases began in 2004 and continued through 2006 during the Fusarium outbreak associated with ReNu with MoistureLoc. Despite the decrease in contact lens–related Fusarium infections, the overall number of fungal keratitis cases remained high through 2008. Fungal keratitis was more often associated with contact lens use than with trauma in this time. Key Words: infectious keratitis, fungal keratitis, contact lens, Fusarium, Candida, fungal ocular infection, ocular mycosis, corneal ulcers agents is not as good as the response of bacterial infections to antibiotics in part because of poor corneal penetration of the antimycotic agents.1 Over the past few years, there have been many reports worldwide of an increased rate of contact lens–related fungal keratitis. The use of ReNu with MoistureLoc (ReNu ML) (Bausch & Lomb, Rochester, NY) contact lens solution was found to be a significant risk factor associated with Fusarium infection.2 The first evidence of the problem was reported in Hong Kong and Singapore, which resulted in the suspension of the sales of this product in these locations in February of 2006.3 This was followed by reports of similar findings sent to the Centers for Disease Control and Prevention by American ophthalmologists in March of the same year. Studies conducted by Alfonso et al,4 Gorscak et al,5 Bernal et al,6 and Jeng et al7 all reported an outbreak of Fusarium keratitis between 2004 and 2006. A multistate outbreak was reported in the Journal of the American Medical Association in which the only significant association found after multivariate analysis was the use of ReNu ML solution.2 Despite the in vitro efficacy of this contact lens solution, it lost its biocidal efficacy in clinical use. It was voluntarily recalled from the market worldwide in May 2006. After the recall of ReNu ML from the market, Jeng et al7 reported 4 cases of contact lens–related Fusarium keratitis, none of which was associated with the recall product. In this study, we evaluated the number of cases, risk factors, treatment, and prognosis of fungal keratitis during the period from April 1999 to the end of 2008, at Wills Eye Institute, to put the recent Fusarium outbreak into a broader context and to update the trends and outcomes of fungal keratitis at our institute since the study by Tanure et al8 10 years ago. (Cornea 2010;29:1406–1411) F ungal keratitis is less common than bacterial keratitis and more devastating. Fungi can penetrate deep into the stroma and through an intact Descemet membrane, gaining access to the anterior chamber. Deep infection can be very hard to eradicate. Furthermore, the response of fungi to antimycotic Received for publication April 3, 2009; revision received January 27, 2010; accepted February 21, 2010. From the Cornea Service, Wills Eye Institute, Department of Ophthalmology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA. Elisabeth J. Cohen, MD, was paid by lawyers representing patients against Bausch & Lomb. Reprints: Elisabeth J. Cohen, Cornea Service, Wills Eye Institute, 840 Walnut St, Suite 920, Philadelphia, PA 19107 (e-mail: ecohen@willseye.org). Copyright Ó 2010 by Lippincott Williams & Wilkins 1406 | www.corneajrnl.com MATERIALS AND METHODS All patients diagnosed with fungal keratitis presenting to the Cornea Service at Wills Eye Institute between April 1, 1999 (this date was chosen to follow the period studied previously by Tanure et al8 at our institute) and December 31, 2008 were identified through a computerized diagnosis code search of our patient database. Institutional review board approval was obtained, and charts were retrospectively reviewed. All patients with culture-positive fungal infection (defined as fungal growth on 2 separate culture media), histopathological diagnosis of fungal keratitis, and culturenegative cases that were diagnosed clinically on the basis of the response to antifungal treatment after failure of antibiotic therapy were included. Cornea  Volume 29, Number 12, December 2010 Cornea  Volume 29, Number 12, December 2010 Demographic data, dates of the onset of symptoms, and referral and diagnosis were noted. Predisposing risk factors were identified, including trauma and contact lens use. Prereferral treatment, visual acuity (VA) at the time of presentation, clinical features, microbiology and/or pathology results, and treatment were analyzed. Visual outcome, recurrent infection, and need for surgery were also evaluated. A Fisher exact test and an exact logistic regression test were used to test whether there was a change in the rate of contact lens–related infections over time (from 1999 to 2008). SAS version 9.2 statistical software (PROC.FREQ) (SAS Institute, Inc, Cary, NC) was used for exact conditional tests. Relative risks for contact lens–related Fusarium keratitis between 2005 and 2006, and 2007 and 2008 were estimated. RESULTS Seventy-eight eyes of 76 patients were identified; 1 patient had an infection in each eye 1 year apart and 1 had simultaneous bilateral infections. Of these, 35 (46.1%) were males and 41 (53.9%) were females. The mean age was 58.0 6 19.3 years (range 19–89 years). The right eye was affected in 27 cases, the left eye in 47 cases, and 2 patients had bilateral infections. Twenty-five patients presented in the summer, 19 in the winter, 15 in the spring, and 19 in the fall. Seven Fusarium keratitis cases presented in the summer, 8 in the winter, 9 in the spring, and 5 in the fall. The number of contact lens–related fungal infections increased beginning in 2004. Before then, the average was 4 cases every year. In 2004, there was a 2-fold increase in the total number of cases, including 3 contact lens–related infections, caused by filamentous fungi (2 Fusarium and 1 Aspergillus). The Fusarium contact lens outbreak peaked in 2005 with 7 contact lens–related cases. An overall increase in fungal infections (15 cases) was also experienced in 2005. Update on Fungal Keratitis This number remained stable in 2006 with 13 cases, 5 of which were contact lens–related filamentous infections (4 Fusarium and 1 Aspergillus). There was a significant increase in contact lens–related Fusarium infections over time (P = 0.021) with the highest numbers in 2005–2006, but no analogous trend over time for Candida (P =1.00) or other fungal infections (P = 0.577) (Table 1). During 2005 and 2006, 6 of 11 contact lens–related Fusarium keratitis cases (54.5%) presented in winter, whereas only 24.3% (19 of 78) of total cases presented in winter. The number of cases with contact lens–related Fusarium keratitis decreased in subsequent years, with only 2 of 25 cases (8%) in 2007 and 2008. The odds of having a contact lens– related Fusarium infection in 2005–2006 compared with 2007–2008 were 4.40 (95% confidence interval of 0.60– 32.50) (P = 0.178). Although there were 10 fungal cases in 2007, the number of contact lens–related infections dropped to 3 cases (2 Fusarium and 1 yeast). One of the Fusarium cases in 2007 was using ReNu ML even though it was taken off the worldwide market in May 2006 and the other was using ReNu Multiplus. In 2008, 6 of 14 patients (46.1%) had contact lens– related fungal infections (1 Candida, 2 Alternaria, 3 Paecilomyces). Both patients with Alternaria keratitis were using ReNu Multipurpose solution, 2 cases with Paecilomyces keratitis were using Optifree Replenish solution (Alcon Laboratories, Inc, Fort Worth, TX), and another Paecilomyces keratitis case was using a generic brand solution manufactured by Bausch & Lomb, Inc. The Food and Drug Administration and Centers for Disease Control and Prevention were notified about these Alternaria and Paecilomyces infections in February 2009. The use of contact lenses was the most common risk factor for fungal keratitis seen in 28 eyes (35.9%). A history of trauma [17 eyes (22.4%)], a history of penetrating keratoplasty TABLE 1. Fungal Infections by Year Fusarium Candida Others Years No. Cases CL related Not CL related CL related Not CL related CL related Not CL related 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Total 1 5 4 3 2 7 12 11 8 14 67*** 1 0 1 0 0 2 7* 4* 2* 0* 17 **P = 0.02 0 2 0 1 0 0 2 3 0 4 12 0 0 0 0 0 0 0 0 1 1 2 **P = 1.000 0 1 1 1 2 2 2 2 4 2 17 0 1 0 0 0 1 0 1 0 5 8 **P = 0.58 0 1 2 1 0 2 1 1 1 2 11 *Odds of having contact lens–related Fusarium infection 4.4 times greater in 2005–2006 (95% confidence interval of 0.60–32.50) compared with subsequent years of 2007–2008. **Statistically significant increase in contact lens–related Fusarium keratitis over time, with the highest numbers in 2005–2006. The number of cases with contact lens–related Fusarium keratitis decreased in subsequent years. No analogous trend over time for Candidiaor other infections. ***Culture-negative cases [11 of 78, (14.1%)] are not included. The diagnosis was confirmed in 3 of 11 culture-negative cases by cultures and/or histopathology of PK specimens. Of these 8 nonconfirmed cases, 1 occurred in 1999, 1 in 2002, 1 in 2003, 2 in 2005, 1 in 2006, and 2 in 2007. CL, contact lens. q 2010 Lippincott Williams & Wilkins www.corneajrnl.com | 1407 Cornea  Volume 29, Number 12, December 2010 Yildiz et al (PK) [12 eyes (15.8%)], and a history of herpetic eye disease [9 eyes (11.5%) (6 herpes simplex and 3 herpes zoster)] were also common risk factors in our series (Table 2). Overall, among 28 contact lens users, almost half of them used group IV soft contact lenses [13 of 28 patients, (46.4%)], made of high water content ionic polymers. Whereas 10 of 28 patients (35.7%) used an unspecified type of soft contact lens, the others used several contact lenses, including Acuvue 2 (12 patients), Acuvue Oasys (2 patients), Acuvue extended wear soft contact lens (1 patient), Focus N & D (1 patient), Hydraclear (1 patient), and rigid gas–permeable contact lens (1 patient). Fusarium was isolated in 17 of 28 (64.3%) contact lens–related infections in this study. Eight of the contact lens patients in this study used ReNu ML. Five patients used ReNu MultiPurpose solution, 1 used Complete Multi purpose solution, and 3 used unspecified multipurpose solutions (Table 3). Most patients had multiple previous diagnoses and were treated with numerous agents before referral. Sixty-eight eyes (87.2%) were on antibiotics. Sixteen eyes (20.5%) were prescribed antiviral medications. Ten eyes (12.8%) were on antifungal treatment. Twenty-nine (37.2%) were using steroids before diagnosis, 4 of which were combination steroid/antibiotics. The clinical presentation of our patients was variable (Table 4). Typical finding of fungal infections were present in 12 eyes (15.4%) with a feathery infiltrate and in 11 eyes (14.1%) with satellite lesions. Nine eyes (11.5%) had an intact epithelium. More than half of the eyes [46 eyes (58.9%)] had nonspecific infiltrates. The mean size of the stromal infiltrates was 9.1 6 11.6 mm2 (range: 0.1–56 mm2). The mean Snellen VA at the time of presentation was 20/800 (range: 20/20 to no light perception), equivalent to a mean logarithm of the minimum angle of resolution (logMAR) VA of 1.6 6 1.1 (range: 0–3). One eye had no light perception and 2 eyes had light perception vision. The mean time from initial presentation elsewhere to referral to our institute was 12.3 days (range: 1–70 days). The mean time lapse between presentation and diagnosis at our institution was 4 6 9 days (range: 0–60 days). Twenty-seven patients (35.5%) were admitted to the hospital for an average of 7.4 6 2.8 days (range: 3–14 days). Sixty-six cases (86.8%) had positive cultures. One was determined to be fungus but was not further identified. Eleven patients were culture negative, but there was a strong clinical evidence of fungal infection with a favorable response to antifungal therapy, after failure of antibiotics. Histopathology was positive for fungal organisms in 3 of these 11 culturenegative patients. Although it is difficult to identify fungal species by histological criteria, periodic acid–Schiff stain disclosed rare fungal elements described as yeast in 2 culturenegative cases. Fusarium, the most common organism, was isolated in 29 of 78 eyes (37.2%), 17 (58.6%) of which were associated with contact lens wear. Other filamentous fungi were isolated in 15 eyes (19.2%). Candida and other yeasts were isolated from 22 eyes (28.2%) (Table 5). Twenty-one of the 78 eyes (26.9%) in this series were treated with a single topical agent, 45 (57.7%) used a combination of topical and systemic antifungal agents, and 12 (15.4%) used a combination of more than one topical agent. Two cases (2.6%) required intracameral injections of antifungal agents. Steroids were used in 8 eyes (10.2%), after a minimum of 14 days of antifungal treatment (average 45.6 days). Before use of voriconazole, amphotericin was the drug of choice for yeast infections including Candida and was used in 17 of 22 cases (77.2%), either alone or in combination with other topical or oral agents. The second most common agent used for yeasts was voriconazole. Natamycin was the most common antifungal agent used empirically in 7 of the 11 culture-negative cases (63.6%) and for 32 of the 44 filamentous infections (72.7%). Use of voriconazole began in 2003 for the treatment of fungal keratitis. Almost half of the infections [34 of the 78 eyes (43.6%)] were treated with voriconazole as either a single topical agent (1% solution) or an oral agent combined with other topical agents. Eighty-five percent (29 of 34) of the eyes treated with voriconazole healed TABLE 2. Risk Factors of Fungal Keratitis Risk Factor 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Total % Contact lens Trauma PK History of HSV/HZV Ocular surface DM Lid anomalies LASIK Neurotrophic K Systemic steroids No risk factor Multiple risk Total no. eyes* 1 1 — — — — — — — — — 1 1 1 2 — — — 2 — — 1 — — 1 4 1 1 1 1 — 1 1 — — 1 — 3 5 — 1 2 — — — — 1 — — — — 4 — — 2 1 — — — — — — — — 3 3 2 1 1 1 — — — — — — 1 8 8 2 — 1 1 — 1 1 1 — 2 2 15 5 5 2 1 1 — 1 — — — — 5 13 3 1 2 1 2 — — — — — 2 1 10 6 2 2 3 2 2 1 1 — — — 5 15 28 17 12 9 7 5 4 3 2 1 4 19 — 35.9 22.4 15.8 11.5 9.2 6.6 5.2 3.9 3.2 1.6 5.2 22.6 — *The number of risk factors might not add up to the number of eyes each year because more than 1 factor may occur in the same patient. DM, diabetes mellitus; HSV, herpes simplex virus; HZV, herpes zoster virus; LASIK, laser in situ keratomeleuis. 1408 | www.corneajrnl.com q 2010 Lippincott Williams & Wilkins Cornea  Volume 29, Number 12, December 2010 Update on Fungal Keratitis TABLE 3. Contact Lens–Related Fungal Keratitis Cases, Risk Factors, and Causative Organisms Year Case Organism Contact Lens 1999 2001 1 2 3 4 5 6 7 Fusarium Fusarium Trichosporum Aspergillus Fusarium Fusarium Fusarium SCL RGP Focus N & D Acuvue EW SCL EW Acuvue 2 Unknown — Unknown Unknown Unknown Unknown Complete +/2 2/2 2/2 2/2 +/2 2/2 2/2 8 9 10 11 12 13 14 Negative Fusarium Fusarium Fusarium Fusarium Fusarium Fusarium Acuvue FR FR Acuvue Acuvue Acuvue Acuvue Unknown ReNu ML ReNu ML Unknown Unknown ReNu ML ReNu ML 2/2 2/2 2/2 — 2/2 2/+ 2/2 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Fusarium Fusarium Fusarium Fusarium Aspergillus Fusarium Fusarium Candida Paecilomyces Altenaria Altenaria Bipolaris Paecilomyces Paecilomyces Conv SCL Acuvue 2 Acuvue 2 Acuvue Oasys SCL Acuvue 2 Hydroclear Unknown Acuvue 2 Oasys Acuvue Unknown Acuvue 2 FR ReNu ML Unknown ReNu ML ReNu ML ReNu ReNu ML ReNu ReNu Optifree replenish ReNu MultiPurpose ReNu MultiPurpose Unknown — Optifree 2/2 2/2 2/2 2/2 2/2 2/2 2/2 2/2 2/+ — 2/+ — — 2/+ 2004 2005 2006 2007 2008 2 2 2 2 2 Solution Overwear/EW Accompanying Conditions Plant trauma Graves Dump truck driver Plant trauma — — A history of herpetic stromal keratitis on topical steroid before infection Dry eye syndrome Pemphigoid — Water exposure (lake) Water exposure (lake) Well water exposure A history of herpetic stromal keratitis on topical steroid before infection Graves Sinus infection Reuse solution — Viral keratoconjunctivitis — Swimming in contacts — — — — Dog scratch — Corneal scratch removing lens Conv, conventional; EW, extended wear; Focus N & D, Focus night and day; FR, frequent replacement; RGP, rigid gas permeable; SCL, soft contact lens. with scaring. Of the remaining 5 eyes treated with voriconazole, 3 required urgent PK and 2 required glue application because of perforation. The average duration of antifungal treatment was 81 6 68.8 days (range: 20 days to 1 year). Intensive topical treatment (hourly during the day and every 2 hours at night) was given for a mean duration of 15 6 10 days (range: 2–45 days). Oral antifungal agents were required in addition to topical treatment in 54 patients (69.2%) because of the presence of deep corneal infection, nonresponsiveness to topical therapy, and/or suspicion of endophthalmitis. The duration of oral therapy ranged from 16 to 185 days (mean, 60 6 41.7 days). The time taken to heal (defined as resolution of infiltrate and epithelial healing) was variable, ranging from 8 to 300 days (mean 56.8 6 51 days). Nine eyes required urgent therapeutic PKs, 6 of which were because of perforation and 3 were because of uncontrolled infection. Recurrence of infection after clinical improvement occurred in 5 patients, 2–7 months after the first infection was diagnosed (average 4.6 months). None of the patients were on antifungal agents in the time of recurrence, and all responded well to antifungal treatment. The median duration q 2010 Lippincott Williams & Wilkins of total treatment was 129 days (range: 60–365 days, not including time off treatment) for patients with recurrences compared with 81 days (range 20–365 days) for patients without recurrent infections. The mean Snellen best-corrected VA at 3 months after institution of treatment was 20/125 (equivalent to logMAR VA of 0.79 6 0.82) compared with average Snellen of 20/800 (equivalent to logMAR 1.6 6 1.1) at presentation. The mean Snellen best-corrected VA was 20/200 (equivalent to logMAR of 1.0) at 3 months after surgery in patients with therapeutic PKs. DISCUSSION Fungal keratitis among soft contact lens wearers increased beginning in 2004.2–7 Before the recent international outbreak of Fusarium keratitis in 2005–2006, the rate of contact lens–associated corneal infections caused by fungal agents ranged from 2% to 20%.9–14 In a comparative series from our institution, the rate of contact lens–associated fungal keratitis increased from 2.2% in the period between 1969 and 197715 to 49.6% in the period between 2004 and 2005.16 After the outbreak of Fusarium keratitis in 2005 and 2006 and the www.corneajrnl.com | 1409 Cornea  Volume 29, Number 12, December 2010 Yildiz et al TABLE 4. The Presenting Features of the Eyes Clinical Presentation No. Eyes (%) Frank epithelial defect Infiltrates Nonspecific Feathery Satellite Immune ring Peripheral infiltrate Hypopyon Anterior chamber reaction Intact epithelium Endothelial plaque Corneal melting Dendritiform epithelial lesion Epitheliopathy Endophthalmitis 57 (73.1) 46 12 11 4 2 28 13 9 8 3 2 2 2 (58.9) (15.4) (14.1) (5.1) (2.6) (35.9) (16.6) (11.5) (10.2) (3.9) (2.6) (2.6) (2.6) recall of ReNu ML, it is important to determine whether or not the outbreak of contact lens–related fungal infections ended and to update the trends and outcomes of fungal keratitis at our institute since the study by Tanure et al8 10 years ago. In our series, although the odds of having a contact lens–related Fusarium infection in 2005–2006 compared with 2007–2008 were 4.40, the difference was not statistically significant probably because of small sample size. Unlike our previous study, where most fungal infections were evenly distributed among the warmer seasons (spring, summer, and fall) and were less common in the winter, the number of patients presenting in the winter in this series (19 patients) was similar to the number in the summer. This change is probably because of the overall increase in contact lens–related fungal infections (33.9%), especially during the Fusarium outbreak. Interestingly, despite the recall of ReNu ML in May of 2006, 2 of the patients with contact lens–related Fusarium infections presenting later in 2006 were still using it, TABLE 5. Culture Results Organism Number Fusarium Alternaria Paecilomyces Aspergillus Curvularia Scedosporium apiospermum Unidentified filamentous Wangiella Total filamentous Candida albicans C. parapsilosis Malassezia furfur Trichosporon Unidentified yeast Total yeasts Unidentified fungus Negative cultures/smears 29 3 3 2 2 2 2 1 44 17 2 1 1 1 22 1 11 1410 | www.corneajrnl.com in addition to one patient who presented in 2007. This underscores the importance of asking patients what solutions they use and educating them to discard solutions that have been withdrawn from the market. Although the index of suspicion was high among ophthalmologists during the Fusarium outbreak, the majority of patients were misdiagnosed at the time of presentation. This finding is similar to our previous study 8 and studies from other institutions.17 The nonspecific nature of the corneal infiltrates, as noted in 58.9% of our patients, makes the diagnosis of fungal keratitis difficult. Twenty-nine patients were treated with steroids or an antibiotic/steroid combination before diagnosis, which exacerbates fungal infections, especially in the absence of antifungal treatment.18–20 Although there is some controversy on the use of topical steroids in the initial management of microbial keratitis,21,22 the possibility of fungal infection must be considered, and we recommend steroids be avoided in the initial management of suspected microbial keratitis before determination of the cause by corneal cultures.23 Eight patients were culture negative and were diagnosed based on clinical appearance and response to antifungal treatment after failing antibiotic treatment. This may be attributed to the deep nature of the infiltrates, which makes it difficult to reach the organisms by corneal scraping and obtain a positive culture. Although including these cases may contribute to selection bias, it gives a more accurate picture of fungal keratitis in a tertiary cornea practice where the cultures may be a negative and the infection not confirmed, if PK is avoided because of a positive response to antifungal treatment. Repeat cultures and biopsies can be helpful in the diagnosis, but they can still be negative in very deep infections.24 Obtaining cultures from the contact lens itself may sometimes give a clue to the possible organisms involved in cases of microbial keratitis in which the corneal cultures are negative.25 Natamycin, alone or in combination with other oral or topical agents, was the most common antifungal medication used in our series, not only because it is the only commercially available topical antifungal agent but also because of its reported efficacy against Fusarium and other filamentous fungi.26 Although high minimum inhibitory concentration of natamycin to the Fusarium sp. has been reported,7 there are no established breakpoints for antifungal minimum inhibitory concentrations in the eye. Voriconazole, a relatively new triazole approved by the Food and Drug Administration for systemic use in 2002, has been shown in several in vitro studies to have the broadest spectrum activity against yeast, dematiaceous, and hyaline filamentous fungi.27–30 In our series, voriconazole, either in oral or in topical form, was used in treating 34 of our patients (43.6%) beginning in 2003. Voriconazole is now often used as the initial antifungal agent because it is our impression that voriconazole is more effective than natamycin, although natamycin is sometimes used because it is commercially available and does not require frequent renewal. In conclusion, fungal keratitis, in general, is still diagnosed at an increased rate despite a decrease in the number of cases of contact lens–related Fusarium infection in 2007– 2008, down to 0–2 cases per year, a number similar to that q 2010 Lippincott Williams & Wilkins Cornea  Volume 29, Number 12, December 2010 before the outbreak. We are particularly concerned with the finding of the occurrence of 5 contact lens–related fungal keratitis caused by unusual fungal organisms, Alternaria and Paecilomyces, in 2008. Despite increased awareness of fungal keratitis and advances in antifungal treatment, fungal keratitis can be associated with severe vision loss. REFERENCES 1. Alfonso EC, Rosa RH, Miller D. Fungal keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea and External Disease: Clinical Diagnosis and Management. 2nd ed. Philadelphia, PA: Elsevier: Mosby; 2005:1101–1113. 2. Chang DC, Grant GB, O’Donell K, et al. Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA. 2006;296: 953–963. 3. Khor WB, Aung T, Saw SM, et al. An outbreak of Fusarium keratitis associated with contact lens wear in Singapore. JAMA. 2006;295:2867–2873. 4. Alfonso EC, Cantu-Dibildox J, Munir WM, et al. Insurgence of Fusarium keratitis associated with contact lens wear. 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Topical and oral voriconazole in the treatment of fungal keratitis. Am J ophthalmol. 2006;143: 151–154. www.corneajrnl.com | 1411