Eye (2009) 23, 1308–1313 & 2009 Macmillan Publishers Limited All rights reserved 0950-222X/09 $32.00 www.nature.com/eye 1 2 CLINICAL STUDY Fungal keratitis in SJ Tuft and AB Tullo the United Kingdom 2003–2005 Abstract Introduction Purpose To describe the incidence and Fungal keratitis is a potentially devastating current management of fungal keratitis in the ocular infection. The true incidence is unknown, United Kingdom. but the figure is likely to vary according to Methods Cases were identified prospectively regional differences in climate, urbanisation, through the British Ophthalmologic and occupation. In tropical and rural areas, Surveillance Unit (BOSU) from December fungi can be the predominant isolate from cases 2003 to November 2005. Questionnaire data of suppurative keratitis, where it is typically the were requested at diagnosis and at 6 months result of filamentary fungal infection following follow-up. Inclusion criteria were a positive trauma.1 The proportion of cases with fungal culture or microsopic proof from a scraping or keratitis who have yeast infection is greater in biopsy, and a normal residence in the United temperate countries where chronic ocular Kingdom. surface disease is the major risk factor.1–13 Results Data were available on 39 confirmed To provide data on the incidence, risk factors cases at diagnosis and 34 cases at follow-up. for infection, current management, and the The minimum average annualised incidence outcome of fungal keratitis in the United was 0.32 (95% CI, 0.24–0.44) cases per million Kingdom, we have performed the first national 1 Department of Clinical individuals. In 22 cases (56%), only Candida prospective survey that was carried over a Ophthalmology, Moorfields was isolated and 14 of these (63%) had prior period of 2 years. This included all cases Eye Hospital NHS Trust, ocular surface disease treated with topical London, UK reported to the British Ophthalmic Surveillance steroid. A filamentary fungus infection was Unit (BOSU).14 2Manchester Royal Eye more common in male patients (P ¼ 0.02), often Hospital NHS Trust, London, following trauma, and the differences in risk Materials and methods UK factors between types of fungal infection was statistically significant (Po0.001). One case This was a 2-year population-based prospective Correspondence: SJ Tuft, had a mixed yeast and filamentary fungus survey of cases through the BOSU monthly Department of Clinical infection. The most frequent initial topical Ophthalmology, reporting card system. At the end of each Moorfields Eye Hospital therapies were amphotericin B (38%) or month, all consultants and associate specialists NHS Foundation Trust, econazole (28%). In addition, oral fluconazole throughout the United Kingdom 162 City Road, was used in 11 (31%) patients and oral (approximately 1100 doctors) were asked to London itraconazole in six (15%). At follow-up, the indicate a new case or confirm that no cases had EC1V 2PD, vision in 15 eyes (44%) was 6/60 including UK o been seen. Case notification was requested for a Tel: þ 02 07 566 2042; three eyes eviscerated. 24-month study period from December 2003 to Fax: þ 02 07 566 2019. Conclusions This study provides data on the November 2005 inclusive. Cases were defined E-mail: Stephen.tuft@ minimum incidence of fungal keratitis in the as any patient with an episode of suppurative ucl.ac.uk United Kingdom. It provides evidence of keratitis from which at least one positive fungal frequent delay in diagnosis after presentation isolate that was not considered to be a Received: 14 January 2008 to eye departments, inconsistent management, Accepted in revised form: contaminant was obtained after culture of 6 September 2008 and poor outcome. Issues that can now be samples of corneal tissue, or a case of Published online: 3 October addressed. suppurative keratitis from which fungal 2008 Eye (2009) 23, 1308–1313; doi:10.1038/eye.2008.298; elements were identified by microscopy of published online 3 October 2008 appropriately stained tissue. There were no age SJ Tuft received a grant from the Iris fund for the restrictions, and patients normally residing administration of this Keywords: fungal keratitis; survey; outside the United Kingdom were excluded. To project keratomycosis; infection maximise recruitment, the aims of the study Fungal keratitis SJ Tuft and AB Tullo 1309 were publicised in special interest groups for corneal in the distribution of categorical variables between yeast disease in the United Kingdom. The protocol was and filamentous groups were compared using Fisher’s reviewed by the BOSU steering committee and the exact test. The Wilcoxon rank-sum test was used to approval was obtained form the Multicentre Research compare ages and grouped visual outcomes. A P-value Ethics Committee. of p0.05 was considered as evidence of significance. Following the notification of a positive case to BOSU, Subgroup analysis of visual outcome according to species the reporting ophthalmologist was sent an incident of fungus was not performed because of the low number questionnaire by the study investigators. Information of cases. requested included suspected risk factors for infection, the nature of the isolate, if a positive culture had been Results obtained, and the initial management. Specific information on a prior history of ocular trauma, In the 24-month study period, 88 incident forms were microbial keratitis, contact lens wear, recent surgery, dry received, of which 49 forms were excluded. Fourteen of eye, persistent epithelial defect, and topical steroid use these 49 forms were errors (ie, ‘false’ reports on patients were requested, with space for additional comments as that did not have fungal infection, or only presumed free text if other local or systemic risk factor were infection), 13 were duplicate reports, and 14 reported present. For this study, a history of a prior corneal graft cases with fungal keratitis did not fulfil the study was considered as ocular surface disease. Outcome data inclusion criteria (ie, they developed disease outside from cases that matched the inclusion criteria were the study period or they were cases referred from outside obtained from a follow-up questionnaire sent to the the United Kingdom). A notification form only was reporting ophthalmologist 6 months after diagnosis. If a received in eight cases, but the initial questionnaire was questionnaire was not returned at least two reminder not returned, and these were considered as ‘potential letters were sent. The incidence was calculated using the cases’. Therefore, a total of 39 eligible questionnaires estimated population (59.9 million) of the United were received at baseline from 31 ophthalmologists in 23 Kingdom (England, Scotland, Wales, and Northern centres, with 21 cases in the first year and 18 in the Ireland) at the midpoint of the study period.15 Ethical second year. Follow-up forms at 6 months were received approval to record the postcode of the normal residence for 34 of the 39 cases. In total, 22 (56%) cases had yeast of cases was not sought and an analysis of distribution of infection, 16 (41%) had filamentary fungal infection, and cases was not attempted. one case (an 88-year-old female patient) had a mixed A single case with mixed fungal infection was infection of penicillium and yeast while applying topical excluded from the subsequent risk analysis. Differences steroid following penetrating keratoplasty (Table 1). The minimum average total annualised incidence was 0.32 per million individuals (95% CI, 0.24–0.44), with 0.19 per Table 1 Types of isolates from 39 cases of fungal keratitis identified prospectively in the United Kingdom the 2-year million (95% CI, 0.13–0.29) having a yeast corneal interval (2003–2005) infection and 0.14 per million (95% CI, 0.09–0.23) having a filamentary fungus corneal infection. During the study Fungal species Number (%) Subtotal period, the average monthly response rate to the BOSU Yeasts reporting system was 78%. Therefore, assuming that all Candida albicans 14 (35) eight incident forms for which a questionnaire was not Candida guilliermondii 1 (2.5) returned (potential cases) were eligible for inclusion, and Candida parapsilosis 3 (7.5) Candida sp.a 5 (12.5) 23 (57.5) accounting for underreporting, the maximum annualised incidence for the study period was 0.50 cases per million Filamentary fungi individuals (95% CI, 0.39–0.64). Aspergillus fumigatus 4 (10) The average interval between presentation to an eye Apergillus flavus 1 (2.5) care service and confirmation of the diagnosis of fungal Aspergillus sp. 2 (5) Fusarium solani 1 (2.5) keratitis was 31 days (median 14 days, range: 0–145). Fusarium dimerum 1 (2.5) There was no difference in distribution of delay in Scedosporium apiospermum 4 (10) diagnosis between the yeast and filamentary fungal Cylindrocarpon sp. 1 (2.5) keratitis groups (P ¼ 0.381). Positive cultures were Penicillium sp. 1 (2.5) obtained in 35 (90%) of the cases (36 isolates); in two Filamentousa 2 (5) 17 (42.5) cases, a yeast was only identified in a smear and in two a Some isolates of Candida were not speciated, and some fungal isolates cases, a filamentous fungus was only identified in a were only identified on microscopy and speciation was, therefore, not possible. One patient had a mixed infection of Candida and filamentary tissue biopsy. Of the 39 cases, 24 (61%) were female and fungus. the right eye was involved in 16 (41%) patients. There Eye Fungal keratitis SJ Tuft and AB Tullo 1310 was an association between gender and type of infection; of infection; one patient with yeast infection was known with yeast infection more common in female patients, to be HIV positive. The data showed that there was a whereas filamentary fungal infection was more common strong association between the species of fungus in male patients (P ¼ 0.02).