keratitis at some point of follow-up in four patients, by anti-HSV and/or anti-HZV serologic titers in the setting of typical herpetic infection exam in Þve patients, and by a dramatic response and resolution of symptoms following antiviral therapy in the setting of clinical Þndings of chronic herpetic infection (corneal hypoesthesia) in ten patients. We strongly suggest to biopsy and analyze scleral tissue by antiHSV and anti-HZV immunoßuorescence to establish a deÞnite diagnosis, especially in cases where clinical Þndings are nonspeciÞc.

7.3.2Mumps Scleritis

Mumps may affect the eye, leading to catarrhal conjunctivitis, punctate epithelial keratitis, or severe stromal keratitis. Occasionally, scleritis, episcleritis, uveitis, optic neuritis, glaucoma, retinitis, and extraocular muscle palsies may occur [219Ð223]. Diagnosis is usually made by the presence of systemic manifestations of mumps, although isolation of virus and rising antibody titers conÞrm the disease. Mumps ocular manifestations usually resolve spontaneously without recurrences. No speciÞc therapy is recommended.

7.4Parasitic Scleritis

Parasites are generally seen by doctors as exotic organisms that infect individuals from underdeveloped countries. However, the increased interchange of people from different parts of the world through international travel, and the improved diagnostic skills of doctors, have contributed to an increased recognition of these microorganisms as the cause of parasitic infections of the ocular structures, including the sclera.

7.4.1Protozoal Scleritis

7.4.1.1 Acanthamoeba

Acanthamoeba is a small amoeba that may be found in soil, contaminated water (distilled water, tap water, well water, hot tube water,

brackish water, swimming pools, water baths, and sea water), contact lenses (hard and soft lenses), and solutions used to rinse contact lenses (tap water, saliva, well water, homemade nonsterile saline) [224]. Scleritis is believed to be unrelated to direct invasion of Acanthamoeba and attributable to an immune-mediated response, of uncertain etiology, triggered by the corneal infection [225].

Acanthamoeba keratitis with or without scleritis is a potentially devastating infection [226, 227]. Patients with keratoscleritis due to Acanthamoeba are usually young, healthy, immunocompetent individuals, with at least one of the following risk factors: (1) history of minor corneal trauma, (2) direct exposure to soil or contaminated ßuids, or (3) contact lens wear [227Ð229]. Scleritis is usually diffuse or nodular, although it may progress to necrotizing, and lead to scleral ectasia [225], and is accompanied by a ring-shaped inÞltrative stromal keratitis [230], sometimes with persistent or recurrent pseudodendritic or punctate epithelial erosions; anterior uveitis rarely with hypopyon also may be present. Herpes simplex keratitis is the initial diagnosis in about 65% of the patients. Standard cultures are usually negative for bacteria, fungi, and viruses and the course is chronic and progressive in spite of treatment with antimicrobial agents. Many patients present with intense ocular pain, usually out of proportion to the stromal keratitis; the pain is probably due to predilection of the amoeba for neural tissue [231].

The diagnosis of keratoscleritis due to Acanthamoeba is usually missed because the infection is uncommon; herpes simplex keratoscleritis is the most frequent misdiagnosis. However, even if the infection is considered initially, diagnosis of Acanthamoeba may still be difÞcult to conÞrm. A provisional diagnosis can be made using the clinical features and confocal microscopy, although a deÞnitive diagnosis requires culture, histology, or identiÞcation of Acanthamoeba deoxyribonucleic acid by polymerase chain reaction. Routine use of tissue diagnosis is recommended, particularly for

patients unresponsive to treatment. SuperÞcial scrapings of the cornea may not include the parasite if it is located only in corneal stroma. Corneal scrapings or corneal and scleral tissue from biopsy may be stained with calcoßuor white stain; [232, 233] GramÕs, Giemsa, Masson trichrome, Gomori methenamine silver, and WrightÕs stains as well as ßuorescent antibodies also may be used [234]. Culture from corneal scrapings or corneoscleral biopsy, or from contact lenses or contact lens solutions, can be done in conßuent layers of coliform bacteria (Escherichia coli, Enterobacter aerogenes, or

Klebsiella pneumoniae) [235]; the specimen may be transferred directly into the plate or may be placed in PageÕs saline solution for transportation, kept at room temperature, and placed in nonnutrient agar with coliform bacteria in the laboratory. Positive cultures have been seen sometimes in as little as 24 h.

Because Acanthamoeba keratoscleritis has a poor prognosis, a meticulous past history, slitlamp examination, smears with calcoßuor white stain and cultures with nonnutrient agar with E. coli from scrapings or biopsy may be contributory to early diagnosis.

Acanthamoeba keratoscleritis therapy is controversial and sometimes unsatisfactory. The microorganism exists in both cyst and trophozoite states, thus requiring extremely prolonged therapy. Topical biguanides are the only effective therapy for the resistant encysted form of the organism in vitro, if not always in vivo. None of the other drugs that have been used meet the requirements of consistent cysticidal activity and may not have therapeutic role. The medical regimen for Acanthamoeba keratoscleritis includes the two topical biguanides that are in use, polyhexamethylene biguanide (PHMB) 0.02Ð0.06% (200Ð600 mg/mol) and chlorexidine 0.02Ð0.2% (200Ð2,000 mg/ml), and 0.1% propamidine isethionate (Brolene) [236]. Oral ketoconazole or itraconazole also may be added. Systemic antiinßammatory drugs should be added in scleritis. Corticosteroid use is controversial. Penetrating keratoplasty with or without scleral debridement may be needed to eradicate persistent active kera-

Fig. 7.11 Necrotizing scleritis in a patient who also developed stromal keratitis, ultimately requiring corneal grafting for perforation. The keratoplasty grew

Acanthamoeba

Fig. 7.12 Additional views of the extent of the necrotizing scleritis in the patient shown in Fig. 7.11

toscleritis despite medical therapy or in actual or threatened corneal perforation.

In our prior series of 172 patients with scleritis [13],onepatienthadscleritisduetoAcanthamoeba (0.58%). The patient was a 51-year-old male with a presumed past history of herpes keratitis who developed a persistent corneal epithelial defect, a suppurative stromal keratitis, and a nodular scleritis in his right eye (Figs. 7.11 and 7.12). Nodular scleritis rapidly progressed to necrotizing scleritis. Review of systems was unrevealing. Corneal scrapings were taken for GramÕs stain and standard cultures, which were negative. Conjunctival and episcleral biopsy showed nongranulomatous inßammation; GramÕs stain was

negative. Progressive corneal thinning necessitated penetrating keratoplasty (Fig. 7.13). Corneal button histopathological examination disclosed numerous basophilic cysts with darkly staining capsules, clear periphery, and darkly staining centers compatible with Acanthamoeba cysts (Fig. 7.14) as well as stromal necrosis. Culture on nonnutrient agar with E. coli identiÞed

Acanthamoeba polyphaga. Therapy with intensive topical 1% propamidine isethionate (Brolene), neomycin, miconazole, and oral ketoconazole was instituted. The postoperative course was complicated by glaucoma. Two weeks after surgery the patient developed progressive graft tissue necrosis with wound leak and further scleral thinning (Fig. 7.15). Penetrating keratoplastywasrepeatedandtherapyforAcanthamoeba keratoscleritis was continued; 2 months later the eye became phthisical.

In our current series of 500 patients with scleritis, one patient had acanthamoeba scleritis (0.2%). The patient was a 60-year-old female who was a soft contact lens wearer for years with daily wear disposable contact lenses. She wore contact lenses overnight. Examination on presentation disclosed a corneal ring abcess with perineural inÞltrates superiorly and temporally in her left cornea and necrotizing scleritis superotemporally. Cultures of corneal scrapings on nonnutrient agar plates overlaid with E. coli were positive for Acanthamoeba. She was treated with chlorexidine 0.02% eye drops, isethionate propamidine 0.1% drops, oral itraconazole, and oral indomethacin. The patient was slowly improving on that treatment for several weeks but eventually the eye became phthisical.

7.4.1.2 Toxoplasmosis

Although the most frequent ocular manifestation in toxoplasmosis is retinochoroiditis, scleritis, and episcleritis occasionally may occur [237Ð 239]. Scleritis in toxoplasmosis, usually associated with retinochoroiditis, is probably the result of scleral extension of severe toxoplasmic retinitis and choroiditis [240]. Either nongranulomatous or granulomatous inßammation of the sclera has been found [240]. Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii;

Fig. 7.13 Same patient as in Figs. 7.11 and 7.12: status postpenetrating keratoplasty

Fig. 7.14 Same patient as in Figs. 7.11 through 7.13: corneal button examination. Note the numerous basophilic cysts with darkly staining capsules, clear periphery, and darkly staining centers (MagniÞcation, ×63; hematoxylinÐeosin stain)

Fig. 7.15 Same patient as in Figs. 7.11 through 7.14: Progressive necrotizing scleritis in spite of aggressive topical and systemic therapy for Acanthamoeba. The eye was eventually enucleated because of an unsightly phthisical eye