Table 7.1 ClassiÞcation of organisms causing infectious scleritis

1. Bacteria Gram-positive cocci Gram-negative rods Mycobacteria

Atypical mycobacteria

Mycobacterium tuberculosis Mycobacterium leprae

Spirochetes

Treponema pallidum Borrelia burgdorferi

Chlamydiae Actinomycetes

Nocardia asteroides

2. Fungi

Filamentous fungi Dimorphic fungi

3.Viruses Herpes zoster

Herpes simplex type I Mumps

4.Parasites

Protozoa

Acanthamoeba

Toxoplasma gondii

Helminths

Toxocara canis

7.1Bacterial Scleritis

7.1.1Gram-Positive Coccus

and Gram-Negative Rod Scleritis

7.1.1.1 Pathogenesis

Bacteria are capable of establishing a focus of infection in the sclera if normal host barriers or defense mechanisms are compromised. The presence of exogenous bacteria in scleral tissue leads to an inßammatory response. Bacterial scleritis is usually the result of scleral extension of primary corneal infections [1Ð6]. Risk factors in these cases include contact lens wear, recent ocular surgery or suture removal, use of topical medications (corticosteroids, beta blockers), neovascular or phacomorphic glaucomas, adnexal disease, corneal tissue devitalization (recurrent attacks of herpes simplex or herpes zoster keratitis, corneal exposure), and debilitating systemic diseases (AIDS, diabetes). However, primary bacterial

scleritis with or without keratitis may occur, in which case they may follow accidental or surgical injury, or a severe endophthalmitis [1, 7Ð18]. Surgical injuries include pterygium excision followed by § irradiation or topical thiotepa, retinal detachment repair with buckling procedures and/ or diathermy, or strabismus surgery.

Scleritis also may be the result of immunemediated scleral or episcleral vascular damage caused by infectious agents. Bacteria, such as

Pseudomonas, Streptococcus, or Staphylococcus, may cause an inßammatory microangiopathy in sclera by inducing immune-mediated responses in the vessel wall, such as formation and deposition of immune complexes containing bacterial products. The scleritis then becomes autoimmune, and thereafter, independent of the presence of the initiating organism.

7.1.1.2 Organisms

Certain bacterial groups are most frequently encountered in scleral infections. These include the Pseudomonadaceae (Pseudomonas), Streptococcaceae (Streptococcus), Micrococcaceae (Staphylococcus), and Enterobacteriaceae (Proteus).

Pseudomonas aeruginosa is the most common cause of exogenous scleral infection. It is usually associated with primary corneal infection and subsequent scleral extension in a compromised host [1Ð4, 6]. It also may appear after pterygium excision followed by either § irradiation or topical thiotepa (reported range, 6 weeks to 10 years) [1, 7, 9Ð11]; persistent bare sclera due to failure of conjunctival regrowth contributes to chronic scleral exposure and subsequent infection [11].

Streptococcus pneumoniae scleritis also has been described as an extension of corneal infection [1] or after pterigium removal followed by § radiation [7]. Staphylococcus aureus [1, 19],

Staphylococcus epidermidis [1], Proteus [14], and Stenotrophomonas malthophilia [15, 17] also have been reported.

7.1.1.3 Management

Bacterial scleritis should be suspected in cases of indolent progressive scleral necrosis with suppuration, especially if there is a history of accidental

trauma, debilitating ocular or systemic disease, chronic topical medication use (including corticosteroids), or surgical procedures. Scrapings for smears (Gram, Giemsa) and cultures (blood agar, chocolate agar, Sabouraud dextrose agar, thioglycollate broth) must be obtained and fortiÞed antibacterial therapy, depending on smear results, must be initiated as soon as possible. Infection around implants used in retinal detachment surgery or around stitches in any type of scleral surgery, mandate removal of the foreign body. If bacterial 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. Biopsied tissue is then bisected and half is transported immediately to the microbiology laboratory for homogenization and culture in the usual medium or PCR. The remaining half is placed in formalin and transported to the pathology laboratory for histopathology with special stains (periodic

acid-Schiff [PAS], Gomori methenamine silver, acid-fast, calcoßuor white) for identiÞcation of infectious agents.

7.1.1.4 Therapy

A classiÞcation of bacteria based on GramÕs stain Þndings from scleral or corneoscleral smears permits organization of therapy (Table 7.2). Aggressive and prolonged topical, subconjunctival, and systemic antibiotics must be instituted, particularly if keratoscleritis occurs. As soon as the bacteria are isolated by culture, therapy may be reÞned with antibiotic sensitivity results. The avascular nature and the tightly bound collagen structure of the sclera and the cornea make these tissues relatively impermeable to topical and systemic antibiotics. Therefore, if the patient is not improving on the topical fortiÞed, subconjunctival, and systemic antibacterial therapy, subpalpebral lavage with continuous irrigation of antibiotics can improve scleral penetration [3]. Topical corticosteroids should not be included in

the initial therapy of bacterial keratoscleritis or scleritis, but may be of beneÞt after several days of aggressive antibiotic therapy if the infection is coming under control, or if the histopathologial study reveals an inßammatory microangiopathy. An exception to this includes Pseudomonas infection because steroid therapy has almost always been associated with persistence and progression of infection. Corticosteroids act as modulators of the inßammatory response associated with the infection which also may be destructive to the sclera. Patients with prolonged corticosteroid therapy must be carefully monitored, particularly if antibiotics are discontinued, because they may have recurrences of the infection [20].

Strong consideration should be given to surgical management if the patient is not improving within the Þrst few days of antibacterial therapy. Surgical procedures include conjunctival resection and cryotherapy to the immediate underlying sclera [1]. Some of the possible mechanisms for efÞcacy of cryotherapy include mechanical destruction of microorganisms, osmotic changes, or disruption of DNA. Cryotherapy may enhance antibiotic penetration through bacterial cell walls or into the sclera as well [5, 21]. Surgical intervention also may include deÞnitive excisional biopsy for therapeutic and isolation purposes. DeÞnitive excisional biopsy includes deep scleral dissection with subsequent scleral graft and/or lamellar or penetrating keratoplasty. If bacteria are not isolated and histopathological study reveals an inßammatory microangiopathy, immune-mediated responses associated with previous bacterial infection or with systemic autoimmune vasculitic diseases must be suspected and therapy with corticosteroids or immunosuppressive agents must be considered; continued antibiotic coverage is recommended.

7.1.1.5 Prognosis

Bacterial scleritis is generally associated with a poor prognosis. Poor penetration of antibiotics into the tightly bound collagen Þbers of the scleral coat may account, at least partially, for that. Tarr and Constable [10, 11] reported one eye with light perception and two eyes enucleated in their series of four patients with Pseudomonas scleritis

complicating pterygium excision with adjunctive b irradiation. The remaining eye, which retained useful vision, was associated with little delay in the institution of aggressive anti-Pseudomonas therapy. Alfonso and coworkers [2], reviewing their series of 3 patients and another series of 9 patients, noted that in 7 of 12 patients with Pseudomonas keratoscleritis who had predisposing conditions, the involved eye was enucleated. Those eyes receiving early, appropriate, and prolonged anti-Pseudomonas therapy, retained useful vision. Farrell and Smith [7] showed the devastating visual outcome (no light perception) of a case with S. pneumoniae keratoscleritis and endophthalmitis that appeared 2 weeks after pterygium excision with b irradiation. They also reported on a patient with Pseudomonas keratoscleritis that appeared 6 weeks after pterygium excision and topical thiotepa therapy; the Þnal visual acuity light perception only. Both patients waited several days after symptoms began before seeking medical care. Reynolds and Alfonso [1] noted that whereas 9 of their 17 cases (52%) of bacterial keratoscleritis were either enucleated or eviscerated, none of the 8 cases of bacterial scleritis required enucleation. These Þndings suggest that isolated bacterial scleritis has a better prognosis than bacterial keratoscleritis, and that early, aggressive, and prolonged appropriate antibacterial therapy may improve Þnal visual acuity. Early diagnosis, therefore, is essential in order to institute early treatment to halt the progression of the corneal and/or scleral bacterial infection.

7.1.1.6 Our Experience

In our prior series of 172 patients with scleritis [13], two patients had primary bacterial scleritis (1.16%). One of these was a 70-year-old white male with GraveÕs ophthalmopathy, diabetes mellitus, hypertension, anemia, and atherosclerotic heart disease, who developed a suppurative necrotizing anterior scleritis and posterior scleritis in his left eye 2 weeks after strabismus surgery [14]. Visual acuity at that time was 20/70. Biopsy of the sclera showed perivascular neutrophilic and lymphocytic inÞltration; GramÕs stain showed gram-negative rods, and periodic acid-Schiff