Scedosporium prolificans Keratouveitis in Association with a Contact Lens Retained Intraocularly over a Long Term

Abstract

Scedosporium prolificans is a soil saprophyte that is associated with a large variety of infectious processes and with respiratory colonization in immunocompetent and immunocompromised patients. We report the first described case of S. prolificans keratouveitis associated with the intraocular long-term retention of a contact lens in a 76-year-old female patient.

CASE REPORT

A 76-year-old female was seen in February 2000 with an 8-week history of acute keratitis of the left eye. Ten years previously, she had started to wear contact lenses to correct her presbyopia. She wore the lenses for 6 months, at which time she apparently lost them and returned to using eyeglasses. Three days later, the right contact lens was found in the patient's right superior conjunctival fornix and removed. The left contact lens was never found and was believed to have been dislodged on its own. However, the patient started to experience a constant feeling of a foreign body in the left eye with lacrimation and discharges. She was diagnosed with keratitis of the left eye of unknown etiology and was started on ciprofloxacin eye drops after Staphylococcus aureus was isolated from the left corneal scrapings. Although the condition improved, it did not resolve completely, and over the course of the next 10 years the patient received medical management periodically, including a variety of antibiotics, topical steroids, and artificial tears for acute exacerbations of chronic keratitis. The most recent exacerbation occurred in December 1999, when the patient was treated with amoxicillin-clavulanate potassium (Augmentin) orally and a 0.3% tobramycin ophthalmic solution (1 drop four times daily).

In February 2000, an examination revealed mild swelling of the left upper eyelid. The eyelid was inverted, and the tarsal border was lifted with a glass rod. A necrotic mass that was easily removed with forceps became visible. The mass had numerous, variously sized, cauliflower-like growths and was covered by a whitish membrane on the superior surface.

A portion of the mass was sent for histological examination. Hematoxylin-and-eosin-stained sections of the mass revealed extensive areas of necrotic tissue surrounding the long-lost contact lens. Lymphocytes and plasma cells had infiltrated the periphery of the necrotic tissue around the lens. Septate hyphae within the necrotic tissue were visualized with Grocott methenamine silver nitrate stain (8) (Fig. 1). Gram-positive bacteria were demonstrated with Brown-Hopps Gram stain (3).

FIG. 1.

(A) Grocott’s methenamine silver nitrate stain demonstrating fungal infiltration of the tissue around the lens. Magnification, ×20. (B) Fungal infiltration of the tissue around the lens at a higher magnification (×40).

The ophthalmologist inoculated a portion of the mass directly onto a Trypticase soy agar plate with 5% sheep blood, a chocolate agar plate, thioglycolate broth (for anaerobic culture), and a Sabouraud dextrose agar slant. None of the mass was submitted for direct examination by Gram staining or KOH staining. Additional specimens were submitted in viral transport medium for herpes simplex virus, cytomegalovirus, and Chlamydia trachomatis cultures. These latter cultures never grew.

Blood and chocolate agar plates grew S. aureus after overnight incubation at 35°C in CO₂. Susceptibility testing, performed with the Vitek GPS-102 card (bioMérieux Vitek, Hazelwood, Mo.), showed the isolate to be susceptible to cefazolin, ciprofloxacin, clindamycin, gentamicin, levofloxacin, methicillin, trimethoprim-sulfamethoxazole, and vancomycin.

Based on the histopathological findings alone, the patient's antibiotics were changed from amoxicillin-clavulanate potassium (Augmentin) and tobramycin to 0.3% ciprofloxacin eye drops, with 1 drop given four times daily. Antifungal agents were not begun. Two days after removal of the mass, the patient was taken for surgical exploration of the superior fornix, which demonstrated an unusually deep fornix free of additional foreign bodies and necrotic material. Subsequent postoperative resolution of the clinical signs of keratitis rapidly followed with ciprofloxacin treatment only. The patient has demonstrated no further episodes of microbial keratitis, and the vision in her left eye has improved to the level that existed prior to wearing contact lenses.

The Sabouraud dextrose agar slant grew 2 colonies of a white mold with hyaline septate hyphae after 4 days of incubation at 25°C in air. The mold was subcultured onto potato dextrose agar and Mycosel agar. The organism grew on both types of media after 5 days of incubation at 25°C. The fungus had whitish colonies that turned dark with age. The organism was identified as Scedosporium prolificans based on hyaline septate hyphae bearing flask-shaped conidiogenous cells with elongated necks and conidia on a potato dextrose agar slide culture stained with lactophenol aniline blue (Fig. 2). No other yeast species or molds grew.

FIG. 2.

S. prolificans. A slide culture stained with lactophenol aniline blue demonstrates flask-shaped conidiogenous cells with elongated necks and individual conidia as well as chains (A) and clusters (B). Magnification, ×40.

Susceptibility testing of the fungus was performed by the University of Texas Health Science Center at San Antonio by use of a broth macrodilution method in accordance with present NCCLS standards. The MICs of amphotericin B, fluconazole, and natamycin (Natacyn) at 48 h were 1, 16, and 32 μg/ml, respectively.

Discussion.

S. prolificans is a human pathogen that was first identified by Malloch and Salkin in 1984 as Scedosporium inflatum, a new species of Scedosporium (15). In 1991, Gueho and de Hoog demonstrated that S. inflatum is identical to Lomentospora prolificans. The species was then renamed S. prolificans (9). This organism is considered to be a soil saprobe. Recovery of S. prolificans from a clinical specimen may indicate true infection or colonization. Immunocompetent hosts tend to have local disease secondary to trauma or surgery, including soft tissue infections, osteomyelitis, arthritis, and endocarditis (5, 6, 14, 15, 21, 23, 25). At the other extreme, neutropenic patients, particularly those with solid organ transplants or hematological malignancies, tend to have disseminated, usually fatal, infections (10, 13, 25). Isolation of S. prolificans from respiratory secretions from immunocompromised, but not neutropenic, patients may or may not represent pulmonary infection (10, 25). Association of S. prolificans with eye diseases is unusual: to our knowledge, only three cases (11, 16, 20) of ocular inflammation due to this fungus have been reported in the English-language literature. Two cases of endophthalmitis due to S. prolificans have also been reported, an intravenous drug abuser requiring enucleation and no antifungal therapy and a leukemia patient in remission who died of disseminated fungal infection (25). Neither of these patients wore contact lenses like our patient did.

We observed an immunocompetent female patient in whom S. prolificans and S. aureus caused keratouveitis facilitated by a long-term-retained contact lens in the left superior fornix. It is not uncommon for a contact lens to become eroded in the ocular soft tissue after prolonged retention in the conjunctival fornix (4). The range of contact lens retention times reported in the literature is 1 day (4) to 12 years (18).

The main factor in the pathogenesis of keratitis associated with wearing contact lenses is the breakdown of the corneal epithelial surface (2). Breakdown may occur as a direct result of insertion and removal of contacts, through chemical interactions with disinfecting solutions, or from wearing the lenses beyond the recommended duration prior to removal. The corneal epithelium becomes less effective as a barrier, which in turn creates an entry port for microorganisms. In addition, mucin and other components of tears enhance the attachment of Pseudomonas aeruginosa to contact lenses (19). Thus, while most trauma-associated corneal ulcers are usually associated with staphylococci and streptococci, contact lens-associated corneal ulcers usually develop secondary to contamination during contact lens care. Thus, it is not surprising that the most frequent organism causing bacterial keratitis in contact lens wearers is P. aeruginosa (7, 19). Fungal keratitis without trauma occurs in less than 4% of cosmetic contact lens-associated ulcers but in 27% of therapeutic contact lens-associated ulcers (19, 22, 24). The increased incidence of infection in patients using therapeutic contact lenses is not surprising since they are already at risk for infection due to their underlying ophthalmologic disease processes. Fungal keratitis without trauma is caused most often by fungi which may colonize the conjunctiva, which include Acremonium, Alternaria, Aspergillus, Candida, Cladosporium, Fusarium, and Penicillium spp. (12, 17, 22, 24). Invasion of the contact lens itself by fungi appears to precede corneal invasion (19, 24). If the cornea is not invaded, removal of the lens resolves the corneal irritation without the use of antifungal agents. If the cornea is invaded, aggressive surgical debridement and appropriate antifungal agents are required to avoid either loss of visual acuity or enucleation (11, 16, 19, 20, 24).

We believe that our patient's left contact lens, which was thought to be self-discharged, became lodged in the left superior fornix. Pressure necrosis followed, resulting in embedment of the lens in the superior orbit, a buildup of necrotic tissue on the lens itself, and subsequent secondary keratitis. Traumatized epithelium secondary to the retained contact lens and a moist environment surrounding a hydrophilic lens led to fungal and bacterial proliferation. Histopathological examination of the specimen demonstrated fungal infiltration of the necrotic tissue around the contact lens. The clinical presentation also supported the diagnosis of fungal keratitis. Although the patient had been treated with antibacterial agents periodically for the preceding 10 years for acute exacerbations of chronic keratitis, the present acute episode lasted for 2 months. We believe that the fungus and the S. aureus were introduced into our patient's eye within the 3 to 4 months prior to her February clinic visit, based on the development of significant symptoms within 4 weeks in the other three cases of S. prolificans keratoscleritis. Only one of the three patients was reported to have sustained a “hit in the eye by a small piece of dirt while gardening” (11, 16, 20). Our patient did not report a similar trauma, but the possibility cannot be ruled out. Alternatively, the fungus may have been introduced by airborne spores or by the lack of appropriate hand washing after contact with soil or plants. Surgical exploration showed that fungal proliferation appeared to be limited to the tissues around the contact lens only, without spread to the adjacent ocular tissues. Therefore, removal of the contact lens facilitated the patient's recovery without the use of antifungal agents. To our knowledge, no association between S. prolificans and contact lenses has been previously reported.

The guidelines for treatment of fungal keratitis recommend 0.1% amphotericin or 5% natamycin as the first-line antifungal agent (1). Natamycin is a broad-spectrum polyene antifungal produced at a concentration of 2,500 μg/drop, according to the manufacturer. One drop is administered every 1 to 2 h for the first 2 to 3 days and then 1 drop is administered six to eight times daily for 14 days to 5 weeks, depending on the organism and the extent of infection. Topical administration provides therapeutic concentrations for the cornea but not the aqueous or vitreous humor (package insert). The natamycin MIC for our S. prolificans isolate was 32 μg/ml, which might have been effective had the infection spread to adjacent tissues since this concentration is six times that provided by the manufacturer.

S. prolificans ocular infections appear to have varied responses to medical therapy (5, 11, 20). Sullivan et al. (20) reported a case of advanced S. prolificans keratoscleritis that responded poorly to intensive topical 0.15% amphotericin B and 5% natamycin plus 100 mg of itraconazole and then 200 mg of ketoconazole, ultimately resulting in enucleation. The organism was reported as being susceptible to natamycin, miconazole, and cotrimazole, intermediate to ketoconazole, and resistant to amphotericin B, itraconazole, fluconazole, and 5-flucytosine, but MICs were not provided. The S. prolificans case reported by Moriarty et al. (16) did not respond to debridement and 3 months of topical natamycin and systemic fluconazole but eventually resolved after treatment with intravenous amphotericin B for 1 month. Susceptibility testing was not reported, although the switch to amphotericin B was based on “microbiological advice.” In contrast, the case of S. prolificans keratoscleritis reported by Kumar et al. (11) was successfully managed with scleral debridement combined with topical natamycin and 200 mg of itraconazole twice a day. Susceptibility testing was not reported. Our patient was successfully managed with surgical debridement and ciprofloxacin alone, based on antibacterial susceptibility testing and the guidelines for treatment of microbial keratitis (1), because infection appeared to be limited to the necrotic mass itself.

In conclusion, prolonged lens retention can facilitate bacterial as well as fungal proliferation around the lens that may allow the development of subsequent infections. In such a case, it would be reasonable at an early stage to consider S. prolificans as a causative factor, to perform appropriate stains and cultures, and to initiate appropriate management, which may or may not include antifungal treatment.