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Fungal keratitis is a rare complication of photorefractive keratectomy (PRK),1,2 LASIK,3–6 and LASIK enhancement.7 We describe a patient who developed keratitis in one eye after bilateral LASIK procedures. The keratitis progressed despite intensive topical and systemic antibacterial and antifungal treatment. Initial cultures were negative, but a diagnosis of fungal keratitis was suggested by confocal microscopy. Fusarium solani was isolated following penetrating keratoplasty.
A 45 year old woman noted blur and discomfort of the right eye 3 days after bilateral LASIK procedures for myopia. The visual acuity was 6/9–3 unaided and there was a 1.5 mm diameter infiltrate beneath the flap (Fig 1A). The left eye was unaffected with an unaided visual acuity of 6/6. Cultures were not taken but her topical antibiotic was changes from chloramphenicol to ofloxacin, and dexamethasone 0.1% four times daily was continued. After a further 4 days the vision had reduced to 6/36 and there was ulceration through the flap over the infiltrate; treatment was changed to hourly gentamicin 1.5%, cefuroxime 5%, and econazole 1%, and dexamethasone was continued to reduce the risk of further flap melt. A culture from the ulcerated corneal surface over the infiltrate was negative. There was continued deterioration and treatment was therefore stopped for 24 hours before the flap was lifted and cultures taken for routine bacteriology, acid fast bacilli (Mycobacterium), and fungi. No organism was identified. Because of the uncertain diagnosis a loading oral dose of fluconazole 200 mg was given followed by 100 mg daily, and a 7 day course of intensive topical vancomycin (5%) and amikacin (2.5%) was started with oral clarithromicin 500 mg twice daily. Confocal microscopy of the edge of the lesion demonstrated filamentary structures in the deep stroma (Fig 1B), but a subsequent tissue biopsy of the flap and the deeper stroma was again negative. Despite intensive treatment with topical amphotericin (0.15%) and natamycin (5%), and courses of oral itraconazole (400 mg daily) and voriconazole (400 mg daily) there was continued deterioration and the cornea perforated (Fig 1C). On the 32nd day following LASIK a 9 mm penetrating corneal graft was performed and the anterior chamber was irrigated with amphotericin (5 μg in 0.1 ml). Dexamethasone 0.1% four times daily was continued after surgery to treat severe intraocular inflammation. Histology of the excised corneal button showed filamentary fungal elements anterior to Descemet’s membrane but no evidence of hyphae extending to the margin of the excised tissue. Fusarium solani was subsequently grown from the corneal button and the isolate was reported sensitive in vitro to amphotericin (1.0 mg/l), partially sensitive to clotrimazole (8 mg/l), econazole (4 mg/l), and miconazole (8 mg/l), and resistant to itraconazole (>16 mg/l) and fluconazole (>16 mg/l). Despite continued topical and oral antifungal treatment, two further penetrating grafts were necessary to remove recurrences at the graft interface. Following the last graft topical steroid was substituted with topical cyclosporin A 2% four times daily for 4 weeks, after which fluoromethalone 0.1% four times daily was started to control inflammation and prevent vascularisation. All topical antifungal treatment was stopped after 3 months. The final vision at 8 months was reduced to 6/60 as a result of irregular corneal astigmatism, cataract, and graft oedema.
Fungal keratitis is rare in the United Kingdom but accounts for 17–37% of microbial keratitis isolates in warmer countries.8 To date all reported cases of fungal keratitis after LASIK have been due to filamentary organisms.3–7 The diagnosis may be difficult to confirm as cultures and biopsies of the anterior stroma can be negative because of the tendency of filamentary fungi to proliferate in the posterior corneal stroma. A delay in identification of the causative agent often contributes to the poor outcome. Of the four previous reported cases of presumed flap interface infection, excisional keratoplasty was required in three,4–6 and perforation and vascularisation of the corneal occurred in one.7 The only case with a medical cure had a surface infection of a persistent epithelial defect.3
The origin of this infection is uncertain. The patient had visited Florida 2 months previously, where Fusarium sp is the most common isolate from cases of fungal keratitis.8 On the day of treatment the ambient temperature in London was 80°F, but subsequent air culture plates from the treatment area and from the air conditioning system were negative. Because of a reluctance to disturb the LASIK flap there is a temptation to treat infiltrates empirically with broad spectrum antibiotics and steroid,4–6 rather than lifting the flap to culture the lesion directly. Unfortunately, in this case, two cultures were negative, and the diagnosis of a filamentary fungal infection was suggested by confocal microscopy.9 A further negative biopsy then delayed a decision for surgical intervention. Corticosteroid may increase the virulence of pathogenic fungi and it is normally contraindicated in fungal keratitis, although it has a role in reducing inflammation after antifungal treatment has been started.8 The role of cyclosporin A as an alternative to steroid after surgery for fungal keratitis requires further evaluation.10
Mr John Dart provided helpful advice with the management of this case.