7.2 Fungal Scleritis

an opportunistic organism usually affecting immunosuppressed patients or patients after trauma [136Ð138]. Systemically, it can involve lungs, brain, kidney, skin, and less commonly other organs, such as heart, liver, spleen, and bone. Ocular manifestations include scleritis, conjunctivitis, keratitis, endophthalmitis, and orbital involvement [139Ð145].

Nocardial scleritis has been reported as necrotizing scleritis after subtenon triamcinolone acetonide injection [140]. It has also been reported as necrotizing scleritis with mucopurulent discharge in association with a silicone scleral buckle due to retinal detachment. In spite of culture isolation and institution of adequate therapy, progression of scleral necrosis could not be halted and the eye was enucleated [143]. Nocardial scleral involvement has also been shown histologically after nocardial endophthalmitis that required evisceration [145].

Diagnosis can be established by histological identiÞcation of the characteristic hyphal forms with GramÕs stain, overstained Gomori methenamine silver stain, or modiÞed acid-fast stain. The latter, coupled with the fact that fragmented hyphae resemble bacillary forms, could lead to an erroneous diagnosis of tuberculosis. Diagnosis also can be established by culture of the bacteria in blood agar or in Sabouraud dextrose agar; the organism may appear in culture after a long period of time (as late as 14 days) [146].

Trimethoprim with sulfamethoxazole is the drug combination of choice. In case of resistance or drug reaction, amikacin or minocycline may be used as an alternative [143].

7.2Fungal Scleritis

Fungal scleritis is a rare entity usually caused by an exogenous infection. Occasionally, however, it may be the result of hematogenous spread of a systemic fungal disease [147]. Fungal scleritis, often associated with keratitis, poses a threat to the eye, not only because of the damage caused by the organism, but also because the available antifungal agents penetrate the sclera poorly.

7.2.1Filamentous and Dimorphic Fungal Scleritis

7.2.1.1 Pathogenesis

As in bacterial scleritis, fungal infections of the sclera often follow an accidental injury, especially with vegetable matter or soil, surgical procedures, such as pterygium excision followed by § irradiation [148] or retinal detachment repair with buckling procedures [149, 150], or panophthalmitis [151]. Debilitating ocular or systemic diseases, contact lens use, intravenous narcotic addiction [147], and chronic topical medication use, including corticosteroids, also are risk factors.

7.2.1.2 Organisms

Fungi are eukaryotic organisms that may be classiÞed as yeasts, molds, and dimorphic. Yeasts are oval structures that grow as single cells and reproduce by asexual budding, producing structures resembling hyphae (pseudohyphae). Molds grow as long multicellular Þlamentous strands (mycelia) that may reproduce either by cellular division or by elaboration of fruiting bodies called sporangia. Some pathogenic fungi are termed dimorphic because they exist as yeast forms in host tissues while behaving as molds in the saprophytic state. The most common fungi that may cause scleritis are the Þlamentous fungi, such as Aspergillus [147, 148, 152], the Acremonium [1], and the Sphaeropsidales (Lasiodiplodia theobromae) [151]. Other less common Þlamentous fungi implicated in scleral infection are Scedosporium [153],

Sporothrix schenckii [154], Paecilomyces [155], Penicillium [156], and Cephalosporium [156].

Rhinosporidium seeberi, an organism of uncertain taxonomic position although most probably a fungus, also may cause scleral ulceration [157].

7.2.1.3 Management

Fungal scleritis should be suspected in cases of slow but progressive scleral necrosis with suppuration, especially if there is a history of accidental trauma (especially involving vegetable matter or soil), debilitating ocular or systemic disease, contact lens use, chronic topical medication use

(including corticosteroids), or surgical procedures. If there is adjacent fungal keratitis, clinical characteristics include feathery borders of a corneal stromal white blood cell inÞltrate, satellite lesions, hypopyon, or endothelial plaque. Infected scleral buckles need to be removed. Material from vigorous scraping of the infected scleral or corneoscleral area with a surgical blade should be smeared onto glass slides for staining (Gram and Giemsa) and onto agar plates or broth for cultures (two blood agar preparations [one kept at room temperature for isolation of fungi, the other at 35¡C for routine culture], chocolate agar, Sauboraud dextrose agar, thioglycollate broth, brainÐheart infusion medium). Because GramÕs stain may identify fungal forms, particularly yeasts (oval structures or pseudohyphae), and alkaline Giemsa and calcoßuor white stains are more likely to show the morphology of Þlamentous fungi (septate hyphal fragments), antifungal therapy must be initiated if the smears detect fungi. If the smears are negative, a topical broadspectrum antibacterial therapy must be instituted.

If fungal infection is the primary clinical suspicion, but smears and cultures (at 48 h) are negative and the patient is not improving on the initial broad-spectrum antibacterial therapy chosen, scleral or corneoscleral biopsy is recommended. Our technique for this includes dissection of conjunctiva, TenonÕs capsule, and episcleral tissue and careful removal of necrotic scleral tissue under the operating microscope (Fig. 7.1). In case of corneal biopsy, we perform a partial thickness trephination with a depth and diameter depending on the corneal area affected, followed by a lamellar dissection. The scleral or corneoscleral biopsy specimen is bisected and half is sent to the microbiology laboratory, where it is placed in 1 ml of meat broth and homogenized with a tissue grinder. One-drop samples are cultured in different media, including blood agar at room temperature, Sabouraud dextrose agar, thioglycollate broth, and brainÐheart infusion medium for fungus isolation. The remaining half is placed in formalin and transported to the pathology laboratory for histopathology with special stains, including PAS, Gomori methenamine silver, and calcoßuor white for fungus identiÞcation.

Anterior chamber paracentesis is indicated in cases of corneoscleral involvement with hypopyon and primary clinical suspicion of fungal keratoscleritis, in which smears, cultures, and scleral or corneoscleral biopsies are negative, and in which no patient improvement on the initial broad-spectrum antibacterial therapy chosen has occurred. The hypopyon present in a patient with bacterial keratitis is a sterile hypopyon, provided the cornea has not perforated. Indeed, performing a paracentesis in a patient with bacterial keratitis carries with it the potential for inoculation of microorganisms into the anterior chamber. However, fungi may invade the anterior chamber through an intact DescemetÕs membrane. Anterior chamber paracentesis must be performed with an adequate-sized needle (usually at least 22 gauge) for vacuuming the hypopyon, through a beveled wound created with a sharp, thin blade. The harvested material should be immediately transported to the microbiology laboratory for culture on blood agar (room temperature), Sabouraud dextrose agar, thyoglycollate broth, and brainÐ heart infusion medium.

As soon as the fungi are identiÞed by culture, therapy may be modiÞed on the basis of results. Because sensitivities of isolated fungi to the various antifungal agents can be determined in only a few specialized centers, such as the Centers for Disease Control (Atlanta, GA), standard antifungal sensitivity studies are generally not performed. However, it is recommended that any fungus isolated be propagated rather than discarded so that additional studies by such centers can be performed in the event the case does not evolve to a cure.

7.2.1.4 Therapy

A deÞnitive diagnosis should be made before starting therapy. In the absence of laboratory conÞrmation, it is best to defer fungal treatment until isolation is achieved, because unusual organisms such as Mycobacterium, Acanthamoeba, or anaerobes could be the etiological agents of scleritis or keratoscleritis.

A classiÞcation of fungi as yeasts and molds, on the basis of smear Þndings, permits organization of therapy (Table 7.2). Aggressive and

prolonged topical, subconjunctival, and oral antifungal treatment must be instituted, particularly if keratoscleritis occurs. More selective antifungal treatment may be indicated after fungus identiÞcation by culture. Medical therapy is limited by the paucity of approved antifungal drugs and by the poor ocular penetration of available agents. Most of the recommendations for treatment are derived largely from uncontrolled clinical studies.

Therapy for conÞrmed fungal scleritis or keratoscleritis is initially medical, although surgery may be required if progressive melting continues in spite of antifungal drug therapy. Surgical intervention may include scleral or keratoscleral excisional biopsy for therapeutic purposes; this procedure may be effective in removing a concentrated abscess and facilitating topical antifungal penetration. DeÞnitive excisional biopsy includes deep scleral dissection, sometimes with subsequent scleral graft and/or lamellar or penetrating keratoplasty after adequate antifungal therapy.

Corticosteroids are contraindicated in fungal scleritis or keratoscleritis because of unequivocal enhancement of fungal growth.

7.2.1.5 Our Experience

In our prior series of 172 patients with scleritis [13], one patient had fungal scleritis (0.58%) (see section on ÒLocal InfectionsÓ in Chap. 5). The patient developed a necrotizing scleritis in his right eye a few days after being struck by a cowÕs tail. Initial cultures were negative but specimens from scleral biopsy stained with Giemsa and Gomori methenamine silver (Fig. 5.33) revealed the presence of fungal forms with septate hyphae forming acute angles, a morphology consistent with Aspergillus. Aspergillus fumigatus was later recovered in culture. Prolonged systemic and topical therapy cured the infection without further further recurrence (Figs. 7.2Ð7.7).

In our current series of 500 patients with scleritis, one patient had fungal scleritis (0.2%). The patient was a 63-year-old male without any prior systemic disease with recurrent superior temporal nodular scleritis in his left eye. Other ocular Þndings were unremarkable. A biopsy was taken from superior scleral nodule; pathohistologic studies,

Fig. 7.2 Extensive necrotizing scleritis in a patient following trauma from a cowÕs tail

Fig. 7.3 Inferior sclera of the same patient as in Fig. 7.2

Fig. 7.4 Same patient as in Figs. 7.2 and 7.3, showing the extensive involvement of the scleritic process, with necrotizing lesions nasally as well as inferiorally and supratemporally

including hematoxylin and eosin, Gram, acid-fast, and Gomori methenamine silver staining did not show any microorganisms, only inßammatory cells. Rheumatologic evaluations, including complete