Six Cases of Scleritis Associated With Systemic Infection Ramzi H e m a d y , M.D., Maite S a i n z de la Maza, M . D . , M i c h a e l B. R a i z m a n , M.D., and C. S t e p h e n Foster, M . D .
Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infectionassociated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mira&i/is-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scierai biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents.
INFECTIONS of the sclera have developed in the following various clinical situations: after scier ai buckling procedures for retinal detach ment1"5; after extension of severe infectious ker atitis, such as that caused by invasion of
Accepted for publication April 22, 1992. From the Immunology Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massa chusetts. This study was supported in part by the Susan M. Hilles Fund, Boston, Massachusetts (Dr. Foster). Reprint requests to Ramzi Hemady, M.D., Department of Ophthalmology, University of Maryland Hospital, 22 S. Greene St., Baltimore, MD 21201.
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Pseudomonas aeruginosa or Acanthamoeba or ganisms into the sclera, which results in corneoscleritis 610 ; as a result of severe endophthalmitis leading to scleritis and panophthalmitis 11 ; as late complications of pterygium excision treated postoperatively with beta radiation 1215 ; and in association with systemic infections such as syphilis and tuberculosis, 11,1620 and sometimes toxoplasmosis. 21 We wanted to determine the prevalence of isolated infection-associated scleritis (without infectious keratitis or endophthalmitis) among patients with scleritis seen at our institution and to study methods of diagnosis and treat ment, and the clinical courses of these patients.
Patients and Methods The records of patients with scleritis seen at our institution between May 1983 and May 1991 were reviewed for causes of infection. For the purposes of this study, infection-associated scleritis was defined as scierai inflammation caused by direct invasion of the sclera with microorganisms, or scierai inflammation result ing from an immune response to a systemic infection. Patients with infectious corneoscleritis or endophthalmitis were excluded. Diagno sis was based on detailed review of systems (cardiovascular, dermatologie, gastrointestinal, genitourinary, neurologic, pulmonary, and rheumatologic), results of careful ocular and physical examination, and results of biopsy, culture, or other laboratory evidence of local or systemic infections. All patients underwent ex tensive immunologie investigations for other causes of scleritis. Six patients met these cri teria for infection-associated scleritis. The records of these patients were located and reviewed. Information regarding patient demo graphics, onset and course of disease, predis posing factors, methods of diagnosis and treat ment, and outcome was recorded.
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Results
Case Reports
Scleritis was diagnosed in 130 patients be tween May 1983 and May 1991. Six of these patients (4.6%) satisfied our study inclusion criteria. Four patients were women, two were men; two were black (both women); the rest were white. Age at initial examination ranged from 55 to 85 years (average, 68 years). All cases were unilateral. In four, scleritis involved the right eye; in two, scleritis involved the left eye. At initial examination, none of the six pa tients had purulent discharge, the typical clini cal sign of infection. Three cases were associat ed with systemic infections. The scleritis was associated with syphilis in Case 1, with toxocariasis in Case 2, and with tuberculosis in Case 4. In all three patients, the systemic infection was diagnosed as a result of studies for the origin of the scleritis. Three cases were associ ated with local infections. Scleritis was associ ated with infection with Proteus mirabilis in Case 3, with infection with herpes zoster virus in Case 6, and with infection with Aspergillus in Case 5. Symptoms started two weeks after an uncomplicated strabismus surgical procedure in the patient in Case 3, 24 hours after blunt ocular trauma in a farm setting in the patient in Case 5, and six months after an episode of ocular herpes zoster in the patient in Case 6. Origin of infection was determined by one or more of the following: serologie testing (Cases 1 and 2); cultures of the conjunctiva (Case 3), sclera (Cases 3 and 5), or sputum (Case 4); medical history (Case 6); tuberculous skin test ing (Case 4); and absence of other possible origins for scleritis in all patients. Examination of a scierai biopsy specimen was essential in determining the origin of scleritis in the pa tients in Cases 3 and 5 (isolation of offending organisms), was an important diagnostic aid in Case 2 (showing absence of tumor cells), and was performed as part of a scierai patch graft in Case 6. All six patients had anterior scleritis (necrotizing, nodular scleritis with inflammation in the patients in Cases 1 and 5, nodular scleritis in the patients in Cases 2 and 3, and necrotizing scleritis with inflammation in the patients in Cases 4 and 6). The patient in Case 3 had concomitant posterior scleritis; the patient in Case 4 had episcleritis in the contralateral eye.
Case 1 A 60-year-old black woman with a two-week history of redness and dull aching pain in the right eye was seen elsewhere on July 29, 1982. Necrotizing, nodular scleritis was diagnosed (Fig. 1), and treatment with prednisolone ace tate 1% and cyclopentolate 1% was begun. Inflammation subsided but recurred three times in the next five months despite treatment with corticosteroid eyedrops, and oral oxyphenbutazone, prednisone, and azathioprine. Results of serologie testing and examination of a scierai biopsy specimen were noncontributory. On May 23, 1983, she was referred to our institu tion. Examination disclosed a visual acuity of R.E.: 20/100 and L.E.: 20/30. The right eye was acutely red and tender with scierai nodules and necrosis. The anterior chamber was uninflamed and the ocular fundus was normal. Results of examination of the left eye were within normal limits. Examination included a detailed review of systems (cardiovascular, dermatologie, gas trointestinal, genitourinary, neurologic, pul monary, and rheumatologic), serologie testing for syphilis, urinalysis, complete blood cell count, and thoracic radiography. All results were within normal limits except for a reactive VDRL test and fluorescent treponemal antibody absorption test; syphilis was diagnosed. Results of cerebrospinal fluid examination were nor mal. Treatment was subsequently begun with
Fig. 1 (Hemady and associates). Case 1. Scierai nodules in the right eye.
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intramuscular administration of 2.4 million units of penicillin G benzathine, once weekly for three weeks; and instillation of prednisolone acetate 1% eyedrops, four times daily and cyclopentolate 1%, three times daily. Ocular inflammation subsequently resolved and visual acuity improved to 2 0 / 4 0 . Over the next four years, the eye remained uninflamed. Case 2 A 70-year-old white woman with a history of recurrent redness, pain, and photophobia in her left eye, and a diagnosis of recurrent nodu lar scleritis and marginal keratitis, was referred to us on July 2, 1987. She had been treated elsewhere with topical neomycin sulfate-polymyxin B sulfate-dexamethasone. At initial ex amination, her visual acuity was R.E.: 20/25 and L.E.: hand motions. Examination of the left eye disclosed temporal nodular scleritis, iritis, a dense cataract, and 360-degree posterior synechiae that precluded adequate examination of the posterior segment of the eye. The right eye was normal. Ultrasonography disclosed a tem poral mass and vitreous membranes in the left eye. Examination disclosed a history of cervical cancer. Because of the patient's age, her history of cervical cancer, and the presence of an intra ocular mass, a metastatic lesion vs a primary ocular melanoma was considered. Extracapsular cataract extraction, sphincterotomy, and pars plana vitrectomy were performed on Aug. 5, 1987, to improve visualization of the posteri or segment. Subsequent ophthalmoscopy dis closed a granuloma temporal to the disk, subretinal exudates, and a fractional detachment of the retina. Biopsy of the scierai nodule and fine-needle biopsy of the intraocular mass were then performed. Tumor cells were absent on pathologic examination of the specimens from either lesion; chronic, nongranulomatous in flammation was noted on examination of the scierai biopsy specimen, and epithelioid cells were noted on examination of the biopsy speci men from the intraocular mass. No organisms were noted in either biopsy specimen, however. An enzyme-linked immunosorbent assay (ELISA) for Toxocara organisms was positive (1:64) and ocular toxocariasis was diagnosed. The patient was subsequently treated with topi cal and systemic corticosteroids. Ocular inflam mation subsided but visual acuity did not im prove, presumably because of the retinal detachment.
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Case 3 A 70-year-old white man with a history of Graves' disease underwent surgical procedures for strabismus (inferior rectus muscle reces sion) in the left eye on Feb. 10, 1988, for hypotropia. Two weeks postoperatively, the pa tient noted discomfort and redness in the left eye. Conjunctivitis was diagnosed (cultures were not performed) and the patient was treat ed with an unknown topical antibiotic. Three weeks later, the eye had worsened with periocular swelling, discharge, chemosis, increased redness, and scierai nodules. At this point (March 24, 1988), the patient was referred with the diagnosis of preseptal cellulitis or scleritis. Visual acuity was R.E.: 20/30 and L.E.: 20/70. The anterior segment appeared as described previously. Ophthalmoscopy showed choroidal folds and effusion. Anterior and posterior scle ritis were suspected and appropriate examina tion was initiated. Examination disclosed (in addition to the history of surgical procedures for strabismus and Graves' disease) diabetes mellitus, hypertension, and atherosclerotic heart disease, all of which were adequately controlled with medicine. Results of detailed laboratory studies were normal. Ultrasono graphy (B-scan) of the left eye showed thicken ing of the choroid and sclera, and choroidal effusion confirming the clinical impression of posterior scleritis. Conjunctival cultures grew Staphylococcus epidermidis. Examination of the scierai biopsy specimen showed neutrophil in vasion of vessel walls and mononuclear perivasculitis. Proteus mirabilis was recovered from cultures of the sclera. Ocular inflammation re sponded promptly to treatment with topical and intravenous vancomycin and gentamicin. Visual acuity in the left eye had improved to 20/30 on April 29, 1988. The eye has remained uninflamed. Case 4 A 55-year-old black Haitian woman with a four-year history of intermittent redness with out marked pain, and gradual decrease in vi sion in the right eye, was referred to us on April 22, 1988. Visual acuity was R.E.: hand motions and L.E.: 20/50. Active scleritis was noted nasally in the right eye with adjacent intersti tial keratitis, and an area of extreme scierai thinning (Fig. 2). A relative afferent pupillary defect was also noted. Episcleritis was present in the left eye. Treatment was begun with pred-
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Fig. 2 (Hemady and associates). Case 4. Scierai thinning with protrusion of uvea and interstitial keratitis in the right eye. nisolone acetate 1% in both eyes and examina tion of scleritis was simultaneously initiated. A purified protein derivative tuberculosis skin test was reactive and the diagnosis of tubercu losis was established by positive sputum stain ing for acid-fast bacilli and recovery of Mycobacterium tuberculosis on culture. The patient was treated for tuberculosis with ethambutol, 1,200 mg/day orally; isoniazid, 300 mg/day orally; rifampin, 600 mg/day orally; and pyridoxine, 50 mg/day orally for six months. Ocu lar inflammation subsided two months after initiation of treatment. Scleritis in the right eye recurred once during the course of systemic treatment but responded promptly to topical prednisolone acetate 1% without further recur rences. Case 5 A 67-year-old white man was working on his farm on Feb. 8, 1990, when he was struck in the right eye by a cow's tail. Twenty-four hours later he developed pain and redness with mild discharge in the right eye and was seen by his ophthalmologist, who diagnosed conjunctivi tis. Treatment with erythromycin ointment, sulfacetamide sodium-prednisolone sodium phosphate drops, and trimethoprim sulfatepolymyxin B sulfate was initiated. Cultures were not performed. The pain and redness increased progressively in the right eye and five days later a scleral/episcleral abscess was not ed. This was surgically drained and the con tents were cultured but no organisms were recovered. On March 8, 1990, immune-mediat ed scierai inflammation was diagnosed pre
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sumptively. Dexamethasone sodium phos phate, 4 mg, was injected subconjunctivally, and treatment with prednisolone acetate 1% eyedrops and dexamethasone sodium phos phate ointment was initiated. The patient was referred to our institution on May 24, 1990, because of worsening inflammation in the right eye. Visual acuity was R.E.: 20/400 and L.E.: 20/30. The right eye was markedly injected, and scierai nodules and necrosis without discharge were noted (Fig. 3). The left eye was normal. Examination disclosed a history of trauma. Aggressive scleritis examination was immediately initiated. Treatment included prednisolone acetate 1% eyedrops, and oral prednisone and indomethacin. Ultrasonography on June 21,1990, did not show posterior scleritis. Because ocular inflammation and pa tient symptoms changed little over the next two weeks, debridement of necrotic sclera and a scierai biopsy were performed. Hyphae were noted on Giemsa stains of the scierai biopsy specimen and aspergilli were later recovered on culture. Pathologic examination of the sclera showed chronic granulomatous perivascular in flammation. Treatment was immediately begun with flucytosine 1% eyedrops, every half hour; amphotericin B 0.15% eyedrops, every hour; fluconazole, 200 mg/day orally; and polymyxin B sulfate-neomycin sulfate-gramicidin oint ment twice a day. Treatment with corticosteroids was discontinued at this point. An inferior retinal detachment was noted on Oct. 25, 1990, despite steady but slow improvement in exter nal ocular inflammation. On Nov. 6, 1990, a new area of scierai necrosis was noted; treat ment was continued unchanged. On Feb. 19,
Fig. 3 (Hemady and associates). Case 5. Intense inflammation, scierai necrosis, and nodules in the right eye.
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1991, scierai inflammation had completely re solved, and the retina was attached. Visual acuity was R.E.: 20/100 and L.E.: 2 0 / 3 0 . Treat ment was slowly tapered and inflammation has not recurred. Case 6 An 85-year-old white woman with discom fort, redness, and decreased vision in the right eye of two weeks' duration was referred to us on June 7, 1990. Visual acuity was R.E.: counting fingers and L.E.: 20/70. Examination of the right eye showed marked inflammation and thinning of the sclera with protrusion of the uvea near the corneoscleral limbus superiorly (Fig. 4). The patient had had an uncomplicated lens extraction and implantation of an intraoc ular lens in the right eye in October 1989, after which she achieved 20/30 visual acuity. Her pes zoster ophthalmicus with iritis and punc tate keratitis of the right eye developed in January 1990; treatment elsewhere with neomycin sulfate-polymyxin B sulfate-dexamethasone eyedrops three times daily, acyclovir 1 g/day orally, and prednisone (unknown dose) orally was started three days after onset of symptoms. Extensive laboratory examination and treatment with prednisolone sodium phos phate 1% eyedrops three times daily, and oral diflunisal, 500 mg twice daily, was initiated. Scleritis secondary to herpes zoster infection was diagnosed on the basis of recent history of herpes zoster ophthalmicus and normal labora tory results. Because of the extensive scierai necrosis, debridement and a scierai patch graft were performed on June 11, 1990 (Fig. 5). Path ologic examination of excised sclera showed granulomatous vasculitis; virus particles were
Fig. 4 (Hemady and associates). Case 6. Scierai/ limbal necrosis and thinning in the right eye.
Fig. 5 (Hemady and associates). Case 6. One month after a scierai patch graft in the right eye. not seen. In December 1990, thinning of the scierai graft (graft ulcération) was noted and treatment with oral methotrexate, 7.5 m g / week, was begun. Thinning of the scierai graft stabilized temporarily but resumed in February 1991 despite continued treatment with metho trexate. The patient was admitted to our institu tion and was treated with pulse intravenous cyclophosphamide. However, scierai thinning progressed, which led to perforation. The right eye lost light perception at this point. Because of the loss in visual acuity and the intense pain, the eye was enucleated.
Discussion The scleritis in 28 of 159 patients (18%) seen over a ten-year period by Watson and Hayreh 22 had an infectious origin. In a clinicopathologic study of necrotizing scleritis by Rao, Marak, and Hidayat, 23 six of 41 cases (15%) were caused by infections. In our study, six of 130 patients (4.6%) with isolated scleritis associated with infections were seen over a seven-year period. This was lower than the prevalence of in fectious scleritis deduced from the studies by Watson and Hayreh 22 and Rao, Marak, and Hidayat. 23 This may have been caused by several important differences between the studies. The definition of infection-associated scleritis may have differed between the studies. Also, the study by Watson and Hayreh 22 covered ten years ending in 1976, whereas our study covered seven years ending in 1991. The two reports were therefore separated by approximately two decades during which the spectrum of infec-
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tious diseases (such as tuberculosis and syphi lis) had changed. Additionally, Watson and Hayreh 22 conducted their study in the United Kingdom, whereas we conducted our study in the United States—two different locales with inherently different spectra of infectious dis eases. The study by Rao, Marak, and Hidayat, 23 although valuable, was limited to a clinicopathologic study of necrotizing scleritis and was not inclusive of all forms of scleritis. Also, the prevalence of infection-related scleritis de termined in our study may not have accurately reflected the prevalence in the general commu nity because of the referral nature of the prac tice from which the patients were drawn. No organism was responsible for more than one case of infection-related scleritis in our series of patients. Case 1 was caused by syphi lis, Case 2 was caused by infection with Toxocara organisms, Case 3 was caused by infection with P. mirabilis and S. epidermidis, Case 4 was caused by tuberculosis, Case 5 was caused by infection with Aspergillus, and Case 6 was caused by herpes zoster. Infective agents may cause scleritis by direct infection of the sclera. Alternatively, infective agents may elicit an autoimmune response that leads to scleritis. In the patient in Case 1, syphilis was diagnosed serologically and con firmed by the response to treatment. The pa tient did not have a history of treatment for syphilis and denied knowledge of syphilis in her medical history. Scleritis in this patient had not responded to anti-inflammatory and immunosuppressive therapy but resolved after ap propriate antimicrobial therapy. The pathogenesis of syphilitic scleritis is unclear. Wilhelmus and Yokoyama17 favored an immune-mediated origin. A possible role for spirochetal infection of the sclera has not been resolved, however. Once syphilis has been diagnosed, cerebrospinal fluid analysis for neurosyphilis must be performed, and treatment with treponemicidal antibiotics is required. If neurosyphilis is diag nosed, appropriate doses of intravenous peni cillin are indicated. 24 Scleritis is an uncommon manifestation of ocular toxocariasis, as in Case 2.25"27 Diagnosis of ocular toxocariasis is usually presumptive and based on medical history (especially in younger patients), typical ocular lesions, and laboratory evaluation including eosinophil count and results of ELISA (a highly specific and reliable test) for antibodies to Toxocara
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organisms. 26 Definitive diagnosis depends on observation of Toxocara larva on pathologic examination. Although the organism was not isolated in the patient in Case 2, and she was beyond the age group normally associated with ocular toxocariasis, we believe that the serolog ie results, the typical granuloma noted on ophthalmoscopy, and the suggestive pathologic characteristics justified the presumptive diag nosis of toxocariasis. Once toxocariasis was diagnosed, treatment with anti-inflammatory agents controlled the ocular inflammation. Scleritis was initially diagnosed and the patient was treated accordingly and was later thought to have an intraocular tumor. Toxocariasis should be added to the differential diagnosis of scleritis and intraocular mass lesions in older individuals. Infections of the sclera have been described after strabismus surgical procedures, as in Case 3.11·28 Scleritis in this patient was anterior and posterior, and purulent discharge was absent; the origin of the scleritis was initially presumed to be an autoimmune response triggered by the recent ocular surgical procedures and examina tion was oriented accordingly. After immuno logie examination had failed to disclose an origin, cultures and biopsy were performed, which disclosed the causative microorganisms, at which time appropriate antimicrobial thera py was begun. The final outcome was satisfac tory, with resolution of scleritis and return to preoperative visual acuity. Examination of scle ritis developing after ocular surgical proce dures must include appropriate cultures even in the absence of typical clinical signs of infection. Scleritis caused by tuberculosis is uncom mon.19,20,29 Donahue 18 described 14 cases of scierai tuberculosis in a tuberculosis sanatori um between 1940 and 1966. More recently, Bloomfield, Mondino, and Gray19 and Nanda, Pflugfelder, and Holland 20 each described a case of scierai tuberculosis. Watson11 saw two patients with tuberculosis who had scleritis at initial examination. We examined an additional patient with scierai tuberculosis (Case 4). Scier ai tuberculosis may be caused by direct scierai invasion with M. tuberculosis (local or hematogenous spread), or may be secondary to an im mune reaction. Mucopurulent discharge, scier ai ulcération, and isolation of M. tuberculosis organisms from ocular tissue may be present in an infection; the inflamed eye may be practical ly painless in an immune reaction. Corneal
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infiltrates and vascularization are usually pres ent in either case. Once tuberculosis has been diagnosed, antituberculous treatment for six to 12 months is begun. 28 Corticosteroids, cycloplegics, and streptomycin may be applied topical ly.19 Scleritis led to the diagnosis of systemic tuberculosis in our patient, demonstrating (as in the patient in Case 1) that scleritis may be the clinical sign of a serious systemic infection at initial examination. Fungal infections of the sclera are uncom mon. Aspergillus-inauced scleritis was diag nosed in the patient in Case 5 after trauma. Stenson, Brookner, and Rosenthal 80 described a patient (intravenous drug abuser) with bilateral endogenous scleritis caused by Aspergillus oryzae.30 Margo, Polack, and Mood14 described a patient with Aspergillus panophthalmitis that complicated beta radiation treatment after pterygium excision. In our patient in Case 5, delay in diagnosis (three months after onset of symp toms) and prolonged use of topical and system ic corticosteroids may have led to delayed re sponse of the scierai infection to antimycotic therapy. Examination of a scierai biopsy speci men was instrumental in establishing the diag nosis of mycotic scleritis. Scleritis in the patient in Case 6 developed six months after an episode of herpes zoster ophthalmicus for which she had been treated with oral acyclovir and prednisone. Scleritis led to scierai thinning for which scierai grafting was required. Scierai inflammation was not con trolled with anti-inflammatory and immunosuppressive agents. Three of 86 patients (4%) with herpes zoster ophthalmicus reviewed by Womack and Liesegang 31 developed scleritis. Scleritis may develop acutely or months after an episode of herpes zoster ophthalmicus and may lead to extensive scierai thinning despite apparently mild inflammation. Herpes zoster scleritis probably has an immunologie origin, and may be accompanied by keratitis or uveitis.31 The differential diagnosis of scleritis must always include local or systemic infections even though the typical clinical signs of ocular infec tion may be lacking. To reach a definitive diag nosis, to initiate appropriate treatment, and to avoid prolonged patient morbidity, examina tion of scleritis should include a detailed re view of systems (cardiovascular, dermatologie, gastrointestinal, genitourinary, neurologic, pulmonary, and rheumatologic) and ocular his
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tory. Appropriate laboratory investigation may then be directed accordingly. Diagnostic scierai biopsy specimen examination may be indicated if the diagnosis remains elusive or if scierai inflammation fails to respond to treatment.
References 1. Lincoff, H. A., McLean, J. M., and Nano, H.: Scierai abscess. I. A complication of retinal detach ment buckling procedures. Arch. Ophthalmol. 74:641, 1965. 2. Milauskas, A. T., and Duke, J. R.: Mycotic scier ai abscess. Report of a case following a scierai buck ling operation for retinal detachment. Am. J. Oph thalmol. 63:951, 1967. 3. Hahn, Y. S., Lincoff, A., Lincoff, H., and Kreissig, I.: Infection after sponge implantation for scierai buckling. Am. J. Ophthalmol. 87:180, 1979. 4. Zinn, K. M., and Ferry, A. P.: Massive scierai necrosis from a Pseudomonas infection following scierai buckling and pars plana vitrectomy surgery. Mt. Sinai J. Med. 47:618, 1980. 5. Lindsey, P. S., Pierce, H., and Welch, R. B.: Removal of scierai buckling elements. Causes and complications. Arch. Ophthalmol. 101:570, 1983. 6. Raber, I. M., Laibson, P. R., Kurz, G. H., and Bernardino, V. B.: Pseudomonas corneoscleral ulcers. Am. J. Ophthalmol. 92:353, 1981. 7. Berler, D. K., and Alper, M. G.: Scierai abscess es and ectasia caused by Pseudomonas aeruginosa. Ann. Ophthalmol. 14:665, 1982. 8. Alfonso, E., Kenyon, K. R., Ormerod, L. D., Ste vens, R., Wagoner, M. D., and Albert, D. M.: Pseudomonas corneoscleritis. Am. J. Ophthalmol. 103:90, 1987. 9. Mannis, M. J., Tamaru, R., Roth, A. M., Burns, M., and Thirkill, C : Acanthamoeba sclerokeratitis. Determining diagnostic criteria. Arch. Ophthalmol. 104:1313, 1986. 10. Reynolds, M. G., and Alfonso, E.: Treatment of infectious scleritis and keratoscleritis. Am. J. Oph thalmol. 112:543, 1991. 11. Watson, P.: Diseases of the sclera and episclera. In Duane, T. D., and Jaeger, E. A. (eds.): Clinical Ophthalmology, vol. 4. Philadelphia, Harp er and Row, 1985, pp. 1-39. 12. Cameron, M. E.: Preventable complications of pterygium excision with beta-irradiation. Br. J. Oph thalmol. 56:52, 1972. 13. Tarr, K. H., and Constable, I. J.: Pseudomonas endophthalmitis associated with scierai necrosis. Br. J. Ophthalmol. 64:676, 1980. 14. Margo, C. E., Polack, F. M., and Mood, C. I.: Aspergillus panophthalmitis complicating treatment of pterygium. Cornea 7:285, 1988. 15. Altman, A. ]., Cohen, E. J., Berger, S. T., and
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Mondino, B. J.: Scleritis and Streptococcus pneumoniae. Cornea 10:341, 1991. 16. Deodati, F., Bec, P., Labro, J. B., and Barrioulet, Y.: Sclerite syphilitique. Aspect clinique et angiographique. Bull. Soc. Ophtalmol. Fr. 71:63, 1971. 17. Wilhelmus, K. R., and Yokoyama, C. M.: Syph ilitic episcleritis and scleritis. Am. J. Ophthalmol. 104:595, 1987. 18. Donahue, H. C : Ophthalmologic experience in a tuberculosis sanatorium. Am. J. Ophthalmol. 64:742, 1967. 19. Bloomfield, S. E., Mondino, B., and Gray, G. F.: Scierai tuberculosis. Arch. Ophthalmol. 94:954, 1976. 20. Nanda, M., Pflugfelder, S. C , and Holland, S.: Mycobacterium tuberculosis scleritis. Am. J. Ophthal mol. 108:736, 1989. 21. Schuman, J. S., Weinberg, R. S., Ferry, A. P., and Guerry, R. K.: Toxoplasmic scleritis. Ophthal mology 95:1399, 1988. 22. Watson, P. G., and Hayreh, S. S.: Scleritis and episcleritis. Br. J. Ophthalmol. 60:163, 1976. 23. Rao, N. A., Marak, G. E., and Hidayat, A. A.: Necrotizing scleritis. A clinico-pathologic study of 41 cases. Ophthalmology 92:1542, 1985. 24. Weinberg, R. S.: Endogenous bacterial and
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fungal infections of the retina and choroid. In Tab bara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, pp. 501-503. 25. Raistrick, E. R., and Dean Hart, J. C. D.: Ocu lar toxocariasis in adults. Br. J. Ophthalmol. 60:365, 1976. 26. Shields, J. A.: Ocular toxocariasis. A review. Surv. Ophthalmol. 28:361, 1984. 27. Tabbara, K. F.: Other parasitic infections. In Tabbara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, pp. 682-688. 28. Jackson, W. B.: Infections of the sclera. In Tab bara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, p. 481. 29. Duke-Elder, S., and Leigh, A. G.: Diseases of the Outer Eye. Cornea and Sclera. In Duke-Elder, S. (ed.): Systems of Ophthalmology, vol. 8, pt. 2. Lon don, Henry Kimpton, 1965, pp. 1024-1033. 30. Stenson, S., Brookner, A., and Rosenthal, S.: Bilateral endogenous necrotizing scleritis due to Aspergillus oryzae. Ann. Ophthalmol. 14:67, 1982. 31. Womack, L. W., and Liesegang, T. J.: Compli cations of herpes zoster ophthalmicus. Arch. Oph thalmol. 101:42, 1983.
Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infectionassociated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mira&i/is-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scierai biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents.
INFECTIONS of the sclera have developed in the following various clinical situations: after scier ai buckling procedures for retinal detach ment1"5; after extension of severe infectious ker atitis, such as that caused by invasion of
Accepted for publication April 22, 1992. From the Immunology Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massa chusetts. This study was supported in part by the Susan M. Hilles Fund, Boston, Massachusetts (Dr. Foster). Reprint requests to Ramzi Hemady, M.D., Department of Ophthalmology, University of Maryland Hospital, 22 S. Greene St., Baltimore, MD 21201.
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Pseudomonas aeruginosa or Acanthamoeba or ganisms into the sclera, which results in corneoscleritis 610 ; as a result of severe endophthalmitis leading to scleritis and panophthalmitis 11 ; as late complications of pterygium excision treated postoperatively with beta radiation 1215 ; and in association with systemic infections such as syphilis and tuberculosis, 11,1620 and sometimes toxoplasmosis. 21 We wanted to determine the prevalence of isolated infection-associated scleritis (without infectious keratitis or endophthalmitis) among patients with scleritis seen at our institution and to study methods of diagnosis and treat ment, and the clinical courses of these patients.
Patients and Methods The records of patients with scleritis seen at our institution between May 1983 and May 1991 were reviewed for causes of infection. For the purposes of this study, infection-associated scleritis was defined as scierai inflammation caused by direct invasion of the sclera with microorganisms, or scierai inflammation result ing from an immune response to a systemic infection. Patients with infectious corneoscleritis or endophthalmitis were excluded. Diagno sis was based on detailed review of systems (cardiovascular, dermatologie, gastrointestinal, genitourinary, neurologic, pulmonary, and rheumatologic), results of careful ocular and physical examination, and results of biopsy, culture, or other laboratory evidence of local or systemic infections. All patients underwent ex tensive immunologie investigations for other causes of scleritis. Six patients met these cri teria for infection-associated scleritis. The records of these patients were located and reviewed. Information regarding patient demo graphics, onset and course of disease, predis posing factors, methods of diagnosis and treat ment, and outcome was recorded.
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Results
Case Reports
Scleritis was diagnosed in 130 patients be tween May 1983 and May 1991. Six of these patients (4.6%) satisfied our study inclusion criteria. Four patients were women, two were men; two were black (both women); the rest were white. Age at initial examination ranged from 55 to 85 years (average, 68 years). All cases were unilateral. In four, scleritis involved the right eye; in two, scleritis involved the left eye. At initial examination, none of the six pa tients had purulent discharge, the typical clini cal sign of infection. Three cases were associat ed with systemic infections. The scleritis was associated with syphilis in Case 1, with toxocariasis in Case 2, and with tuberculosis in Case 4. In all three patients, the systemic infection was diagnosed as a result of studies for the origin of the scleritis. Three cases were associ ated with local infections. Scleritis was associ ated with infection with Proteus mirabilis in Case 3, with infection with herpes zoster virus in Case 6, and with infection with Aspergillus in Case 5. Symptoms started two weeks after an uncomplicated strabismus surgical procedure in the patient in Case 3, 24 hours after blunt ocular trauma in a farm setting in the patient in Case 5, and six months after an episode of ocular herpes zoster in the patient in Case 6. Origin of infection was determined by one or more of the following: serologie testing (Cases 1 and 2); cultures of the conjunctiva (Case 3), sclera (Cases 3 and 5), or sputum (Case 4); medical history (Case 6); tuberculous skin test ing (Case 4); and absence of other possible origins for scleritis in all patients. Examination of a scierai biopsy specimen was essential in determining the origin of scleritis in the pa tients in Cases 3 and 5 (isolation of offending organisms), was an important diagnostic aid in Case 2 (showing absence of tumor cells), and was performed as part of a scierai patch graft in Case 6. All six patients had anterior scleritis (necrotizing, nodular scleritis with inflammation in the patients in Cases 1 and 5, nodular scleritis in the patients in Cases 2 and 3, and necrotizing scleritis with inflammation in the patients in Cases 4 and 6). The patient in Case 3 had concomitant posterior scleritis; the patient in Case 4 had episcleritis in the contralateral eye.
Case 1 A 60-year-old black woman with a two-week history of redness and dull aching pain in the right eye was seen elsewhere on July 29, 1982. Necrotizing, nodular scleritis was diagnosed (Fig. 1), and treatment with prednisolone ace tate 1% and cyclopentolate 1% was begun. Inflammation subsided but recurred three times in the next five months despite treatment with corticosteroid eyedrops, and oral oxyphenbutazone, prednisone, and azathioprine. Results of serologie testing and examination of a scierai biopsy specimen were noncontributory. On May 23, 1983, she was referred to our institu tion. Examination disclosed a visual acuity of R.E.: 20/100 and L.E.: 20/30. The right eye was acutely red and tender with scierai nodules and necrosis. The anterior chamber was uninflamed and the ocular fundus was normal. Results of examination of the left eye were within normal limits. Examination included a detailed review of systems (cardiovascular, dermatologie, gas trointestinal, genitourinary, neurologic, pul monary, and rheumatologic), serologie testing for syphilis, urinalysis, complete blood cell count, and thoracic radiography. All results were within normal limits except for a reactive VDRL test and fluorescent treponemal antibody absorption test; syphilis was diagnosed. Results of cerebrospinal fluid examination were nor mal. Treatment was subsequently begun with
Fig. 1 (Hemady and associates). Case 1. Scierai nodules in the right eye.
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intramuscular administration of 2.4 million units of penicillin G benzathine, once weekly for three weeks; and instillation of prednisolone acetate 1% eyedrops, four times daily and cyclopentolate 1%, three times daily. Ocular inflammation subsequently resolved and visual acuity improved to 2 0 / 4 0 . Over the next four years, the eye remained uninflamed. Case 2 A 70-year-old white woman with a history of recurrent redness, pain, and photophobia in her left eye, and a diagnosis of recurrent nodu lar scleritis and marginal keratitis, was referred to us on July 2, 1987. She had been treated elsewhere with topical neomycin sulfate-polymyxin B sulfate-dexamethasone. At initial ex amination, her visual acuity was R.E.: 20/25 and L.E.: hand motions. Examination of the left eye disclosed temporal nodular scleritis, iritis, a dense cataract, and 360-degree posterior synechiae that precluded adequate examination of the posterior segment of the eye. The right eye was normal. Ultrasonography disclosed a tem poral mass and vitreous membranes in the left eye. Examination disclosed a history of cervical cancer. Because of the patient's age, her history of cervical cancer, and the presence of an intra ocular mass, a metastatic lesion vs a primary ocular melanoma was considered. Extracapsular cataract extraction, sphincterotomy, and pars plana vitrectomy were performed on Aug. 5, 1987, to improve visualization of the posteri or segment. Subsequent ophthalmoscopy dis closed a granuloma temporal to the disk, subretinal exudates, and a fractional detachment of the retina. Biopsy of the scierai nodule and fine-needle biopsy of the intraocular mass were then performed. Tumor cells were absent on pathologic examination of the specimens from either lesion; chronic, nongranulomatous in flammation was noted on examination of the scierai biopsy specimen, and epithelioid cells were noted on examination of the biopsy speci men from the intraocular mass. No organisms were noted in either biopsy specimen, however. An enzyme-linked immunosorbent assay (ELISA) for Toxocara organisms was positive (1:64) and ocular toxocariasis was diagnosed. The patient was subsequently treated with topi cal and systemic corticosteroids. Ocular inflam mation subsided but visual acuity did not im prove, presumably because of the retinal detachment.
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Case 3 A 70-year-old white man with a history of Graves' disease underwent surgical procedures for strabismus (inferior rectus muscle reces sion) in the left eye on Feb. 10, 1988, for hypotropia. Two weeks postoperatively, the pa tient noted discomfort and redness in the left eye. Conjunctivitis was diagnosed (cultures were not performed) and the patient was treat ed with an unknown topical antibiotic. Three weeks later, the eye had worsened with periocular swelling, discharge, chemosis, increased redness, and scierai nodules. At this point (March 24, 1988), the patient was referred with the diagnosis of preseptal cellulitis or scleritis. Visual acuity was R.E.: 20/30 and L.E.: 20/70. The anterior segment appeared as described previously. Ophthalmoscopy showed choroidal folds and effusion. Anterior and posterior scle ritis were suspected and appropriate examina tion was initiated. Examination disclosed (in addition to the history of surgical procedures for strabismus and Graves' disease) diabetes mellitus, hypertension, and atherosclerotic heart disease, all of which were adequately controlled with medicine. Results of detailed laboratory studies were normal. Ultrasono graphy (B-scan) of the left eye showed thicken ing of the choroid and sclera, and choroidal effusion confirming the clinical impression of posterior scleritis. Conjunctival cultures grew Staphylococcus epidermidis. Examination of the scierai biopsy specimen showed neutrophil in vasion of vessel walls and mononuclear perivasculitis. Proteus mirabilis was recovered from cultures of the sclera. Ocular inflammation re sponded promptly to treatment with topical and intravenous vancomycin and gentamicin. Visual acuity in the left eye had improved to 20/30 on April 29, 1988. The eye has remained uninflamed. Case 4 A 55-year-old black Haitian woman with a four-year history of intermittent redness with out marked pain, and gradual decrease in vi sion in the right eye, was referred to us on April 22, 1988. Visual acuity was R.E.: hand motions and L.E.: 20/50. Active scleritis was noted nasally in the right eye with adjacent intersti tial keratitis, and an area of extreme scierai thinning (Fig. 2). A relative afferent pupillary defect was also noted. Episcleritis was present in the left eye. Treatment was begun with pred-
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Fig. 2 (Hemady and associates). Case 4. Scierai thinning with protrusion of uvea and interstitial keratitis in the right eye. nisolone acetate 1% in both eyes and examina tion of scleritis was simultaneously initiated. A purified protein derivative tuberculosis skin test was reactive and the diagnosis of tubercu losis was established by positive sputum stain ing for acid-fast bacilli and recovery of Mycobacterium tuberculosis on culture. The patient was treated for tuberculosis with ethambutol, 1,200 mg/day orally; isoniazid, 300 mg/day orally; rifampin, 600 mg/day orally; and pyridoxine, 50 mg/day orally for six months. Ocu lar inflammation subsided two months after initiation of treatment. Scleritis in the right eye recurred once during the course of systemic treatment but responded promptly to topical prednisolone acetate 1% without further recur rences. Case 5 A 67-year-old white man was working on his farm on Feb. 8, 1990, when he was struck in the right eye by a cow's tail. Twenty-four hours later he developed pain and redness with mild discharge in the right eye and was seen by his ophthalmologist, who diagnosed conjunctivi tis. Treatment with erythromycin ointment, sulfacetamide sodium-prednisolone sodium phosphate drops, and trimethoprim sulfatepolymyxin B sulfate was initiated. Cultures were not performed. The pain and redness increased progressively in the right eye and five days later a scleral/episcleral abscess was not ed. This was surgically drained and the con tents were cultured but no organisms were recovered. On March 8, 1990, immune-mediat ed scierai inflammation was diagnosed pre
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sumptively. Dexamethasone sodium phos phate, 4 mg, was injected subconjunctivally, and treatment with prednisolone acetate 1% eyedrops and dexamethasone sodium phos phate ointment was initiated. The patient was referred to our institution on May 24, 1990, because of worsening inflammation in the right eye. Visual acuity was R.E.: 20/400 and L.E.: 20/30. The right eye was markedly injected, and scierai nodules and necrosis without discharge were noted (Fig. 3). The left eye was normal. Examination disclosed a history of trauma. Aggressive scleritis examination was immediately initiated. Treatment included prednisolone acetate 1% eyedrops, and oral prednisone and indomethacin. Ultrasonography on June 21,1990, did not show posterior scleritis. Because ocular inflammation and pa tient symptoms changed little over the next two weeks, debridement of necrotic sclera and a scierai biopsy were performed. Hyphae were noted on Giemsa stains of the scierai biopsy specimen and aspergilli were later recovered on culture. Pathologic examination of the sclera showed chronic granulomatous perivascular in flammation. Treatment was immediately begun with flucytosine 1% eyedrops, every half hour; amphotericin B 0.15% eyedrops, every hour; fluconazole, 200 mg/day orally; and polymyxin B sulfate-neomycin sulfate-gramicidin oint ment twice a day. Treatment with corticosteroids was discontinued at this point. An inferior retinal detachment was noted on Oct. 25, 1990, despite steady but slow improvement in exter nal ocular inflammation. On Nov. 6, 1990, a new area of scierai necrosis was noted; treat ment was continued unchanged. On Feb. 19,
Fig. 3 (Hemady and associates). Case 5. Intense inflammation, scierai necrosis, and nodules in the right eye.
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1991, scierai inflammation had completely re solved, and the retina was attached. Visual acuity was R.E.: 20/100 and L.E.: 2 0 / 3 0 . Treat ment was slowly tapered and inflammation has not recurred. Case 6 An 85-year-old white woman with discom fort, redness, and decreased vision in the right eye of two weeks' duration was referred to us on June 7, 1990. Visual acuity was R.E.: counting fingers and L.E.: 20/70. Examination of the right eye showed marked inflammation and thinning of the sclera with protrusion of the uvea near the corneoscleral limbus superiorly (Fig. 4). The patient had had an uncomplicated lens extraction and implantation of an intraoc ular lens in the right eye in October 1989, after which she achieved 20/30 visual acuity. Her pes zoster ophthalmicus with iritis and punc tate keratitis of the right eye developed in January 1990; treatment elsewhere with neomycin sulfate-polymyxin B sulfate-dexamethasone eyedrops three times daily, acyclovir 1 g/day orally, and prednisone (unknown dose) orally was started three days after onset of symptoms. Extensive laboratory examination and treatment with prednisolone sodium phos phate 1% eyedrops three times daily, and oral diflunisal, 500 mg twice daily, was initiated. Scleritis secondary to herpes zoster infection was diagnosed on the basis of recent history of herpes zoster ophthalmicus and normal labora tory results. Because of the extensive scierai necrosis, debridement and a scierai patch graft were performed on June 11, 1990 (Fig. 5). Path ologic examination of excised sclera showed granulomatous vasculitis; virus particles were
Fig. 4 (Hemady and associates). Case 6. Scierai/ limbal necrosis and thinning in the right eye.
Fig. 5 (Hemady and associates). Case 6. One month after a scierai patch graft in the right eye. not seen. In December 1990, thinning of the scierai graft (graft ulcération) was noted and treatment with oral methotrexate, 7.5 m g / week, was begun. Thinning of the scierai graft stabilized temporarily but resumed in February 1991 despite continued treatment with metho trexate. The patient was admitted to our institu tion and was treated with pulse intravenous cyclophosphamide. However, scierai thinning progressed, which led to perforation. The right eye lost light perception at this point. Because of the loss in visual acuity and the intense pain, the eye was enucleated.
Discussion The scleritis in 28 of 159 patients (18%) seen over a ten-year period by Watson and Hayreh 22 had an infectious origin. In a clinicopathologic study of necrotizing scleritis by Rao, Marak, and Hidayat, 23 six of 41 cases (15%) were caused by infections. In our study, six of 130 patients (4.6%) with isolated scleritis associated with infections were seen over a seven-year period. This was lower than the prevalence of in fectious scleritis deduced from the studies by Watson and Hayreh 22 and Rao, Marak, and Hidayat. 23 This may have been caused by several important differences between the studies. The definition of infection-associated scleritis may have differed between the studies. Also, the study by Watson and Hayreh 22 covered ten years ending in 1976, whereas our study covered seven years ending in 1991. The two reports were therefore separated by approximately two decades during which the spectrum of infec-
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tious diseases (such as tuberculosis and syphi lis) had changed. Additionally, Watson and Hayreh 22 conducted their study in the United Kingdom, whereas we conducted our study in the United States—two different locales with inherently different spectra of infectious dis eases. The study by Rao, Marak, and Hidayat, 23 although valuable, was limited to a clinicopathologic study of necrotizing scleritis and was not inclusive of all forms of scleritis. Also, the prevalence of infection-related scleritis de termined in our study may not have accurately reflected the prevalence in the general commu nity because of the referral nature of the prac tice from which the patients were drawn. No organism was responsible for more than one case of infection-related scleritis in our series of patients. Case 1 was caused by syphi lis, Case 2 was caused by infection with Toxocara organisms, Case 3 was caused by infection with P. mirabilis and S. epidermidis, Case 4 was caused by tuberculosis, Case 5 was caused by infection with Aspergillus, and Case 6 was caused by herpes zoster. Infective agents may cause scleritis by direct infection of the sclera. Alternatively, infective agents may elicit an autoimmune response that leads to scleritis. In the patient in Case 1, syphilis was diagnosed serologically and con firmed by the response to treatment. The pa tient did not have a history of treatment for syphilis and denied knowledge of syphilis in her medical history. Scleritis in this patient had not responded to anti-inflammatory and immunosuppressive therapy but resolved after ap propriate antimicrobial therapy. The pathogenesis of syphilitic scleritis is unclear. Wilhelmus and Yokoyama17 favored an immune-mediated origin. A possible role for spirochetal infection of the sclera has not been resolved, however. Once syphilis has been diagnosed, cerebrospinal fluid analysis for neurosyphilis must be performed, and treatment with treponemicidal antibiotics is required. If neurosyphilis is diag nosed, appropriate doses of intravenous peni cillin are indicated. 24 Scleritis is an uncommon manifestation of ocular toxocariasis, as in Case 2.25"27 Diagnosis of ocular toxocariasis is usually presumptive and based on medical history (especially in younger patients), typical ocular lesions, and laboratory evaluation including eosinophil count and results of ELISA (a highly specific and reliable test) for antibodies to Toxocara
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organisms. 26 Definitive diagnosis depends on observation of Toxocara larva on pathologic examination. Although the organism was not isolated in the patient in Case 2, and she was beyond the age group normally associated with ocular toxocariasis, we believe that the serolog ie results, the typical granuloma noted on ophthalmoscopy, and the suggestive pathologic characteristics justified the presumptive diag nosis of toxocariasis. Once toxocariasis was diagnosed, treatment with anti-inflammatory agents controlled the ocular inflammation. Scleritis was initially diagnosed and the patient was treated accordingly and was later thought to have an intraocular tumor. Toxocariasis should be added to the differential diagnosis of scleritis and intraocular mass lesions in older individuals. Infections of the sclera have been described after strabismus surgical procedures, as in Case 3.11·28 Scleritis in this patient was anterior and posterior, and purulent discharge was absent; the origin of the scleritis was initially presumed to be an autoimmune response triggered by the recent ocular surgical procedures and examina tion was oriented accordingly. After immuno logie examination had failed to disclose an origin, cultures and biopsy were performed, which disclosed the causative microorganisms, at which time appropriate antimicrobial thera py was begun. The final outcome was satisfac tory, with resolution of scleritis and return to preoperative visual acuity. Examination of scle ritis developing after ocular surgical proce dures must include appropriate cultures even in the absence of typical clinical signs of infection. Scleritis caused by tuberculosis is uncom mon.19,20,29 Donahue 18 described 14 cases of scierai tuberculosis in a tuberculosis sanatori um between 1940 and 1966. More recently, Bloomfield, Mondino, and Gray19 and Nanda, Pflugfelder, and Holland 20 each described a case of scierai tuberculosis. Watson11 saw two patients with tuberculosis who had scleritis at initial examination. We examined an additional patient with scierai tuberculosis (Case 4). Scier ai tuberculosis may be caused by direct scierai invasion with M. tuberculosis (local or hematogenous spread), or may be secondary to an im mune reaction. Mucopurulent discharge, scier ai ulcération, and isolation of M. tuberculosis organisms from ocular tissue may be present in an infection; the inflamed eye may be practical ly painless in an immune reaction. Corneal
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infiltrates and vascularization are usually pres ent in either case. Once tuberculosis has been diagnosed, antituberculous treatment for six to 12 months is begun. 28 Corticosteroids, cycloplegics, and streptomycin may be applied topical ly.19 Scleritis led to the diagnosis of systemic tuberculosis in our patient, demonstrating (as in the patient in Case 1) that scleritis may be the clinical sign of a serious systemic infection at initial examination. Fungal infections of the sclera are uncom mon. Aspergillus-inauced scleritis was diag nosed in the patient in Case 5 after trauma. Stenson, Brookner, and Rosenthal 80 described a patient (intravenous drug abuser) with bilateral endogenous scleritis caused by Aspergillus oryzae.30 Margo, Polack, and Mood14 described a patient with Aspergillus panophthalmitis that complicated beta radiation treatment after pterygium excision. In our patient in Case 5, delay in diagnosis (three months after onset of symp toms) and prolonged use of topical and system ic corticosteroids may have led to delayed re sponse of the scierai infection to antimycotic therapy. Examination of a scierai biopsy speci men was instrumental in establishing the diag nosis of mycotic scleritis. Scleritis in the patient in Case 6 developed six months after an episode of herpes zoster ophthalmicus for which she had been treated with oral acyclovir and prednisone. Scleritis led to scierai thinning for which scierai grafting was required. Scierai inflammation was not con trolled with anti-inflammatory and immunosuppressive agents. Three of 86 patients (4%) with herpes zoster ophthalmicus reviewed by Womack and Liesegang 31 developed scleritis. Scleritis may develop acutely or months after an episode of herpes zoster ophthalmicus and may lead to extensive scierai thinning despite apparently mild inflammation. Herpes zoster scleritis probably has an immunologie origin, and may be accompanied by keratitis or uveitis.31 The differential diagnosis of scleritis must always include local or systemic infections even though the typical clinical signs of ocular infec tion may be lacking. To reach a definitive diag nosis, to initiate appropriate treatment, and to avoid prolonged patient morbidity, examina tion of scleritis should include a detailed re view of systems (cardiovascular, dermatologie, gastrointestinal, genitourinary, neurologic, pulmonary, and rheumatologic) and ocular his
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tory. Appropriate laboratory investigation may then be directed accordingly. Diagnostic scierai biopsy specimen examination may be indicated if the diagnosis remains elusive or if scierai inflammation fails to respond to treatment.
References 1. Lincoff, H. A., McLean, J. M., and Nano, H.: Scierai abscess. I. A complication of retinal detach ment buckling procedures. Arch. Ophthalmol. 74:641, 1965. 2. Milauskas, A. T., and Duke, J. R.: Mycotic scier ai abscess. Report of a case following a scierai buck ling operation for retinal detachment. Am. J. Oph thalmol. 63:951, 1967. 3. Hahn, Y. S., Lincoff, A., Lincoff, H., and Kreissig, I.: Infection after sponge implantation for scierai buckling. Am. J. Ophthalmol. 87:180, 1979. 4. Zinn, K. M., and Ferry, A. P.: Massive scierai necrosis from a Pseudomonas infection following scierai buckling and pars plana vitrectomy surgery. Mt. Sinai J. Med. 47:618, 1980. 5. Lindsey, P. S., Pierce, H., and Welch, R. B.: Removal of scierai buckling elements. Causes and complications. Arch. Ophthalmol. 101:570, 1983. 6. Raber, I. M., Laibson, P. R., Kurz, G. H., and Bernardino, V. B.: Pseudomonas corneoscleral ulcers. Am. J. Ophthalmol. 92:353, 1981. 7. Berler, D. K., and Alper, M. G.: Scierai abscess es and ectasia caused by Pseudomonas aeruginosa. Ann. Ophthalmol. 14:665, 1982. 8. Alfonso, E., Kenyon, K. R., Ormerod, L. D., Ste vens, R., Wagoner, M. D., and Albert, D. M.: Pseudomonas corneoscleritis. Am. J. Ophthalmol. 103:90, 1987. 9. Mannis, M. J., Tamaru, R., Roth, A. M., Burns, M., and Thirkill, C : Acanthamoeba sclerokeratitis. Determining diagnostic criteria. Arch. Ophthalmol. 104:1313, 1986. 10. Reynolds, M. G., and Alfonso, E.: Treatment of infectious scleritis and keratoscleritis. Am. J. Oph thalmol. 112:543, 1991. 11. Watson, P.: Diseases of the sclera and episclera. In Duane, T. D., and Jaeger, E. A. (eds.): Clinical Ophthalmology, vol. 4. Philadelphia, Harp er and Row, 1985, pp. 1-39. 12. Cameron, M. E.: Preventable complications of pterygium excision with beta-irradiation. Br. J. Oph thalmol. 56:52, 1972. 13. Tarr, K. H., and Constable, I. J.: Pseudomonas endophthalmitis associated with scierai necrosis. Br. J. Ophthalmol. 64:676, 1980. 14. Margo, C. E., Polack, F. M., and Mood, C. I.: Aspergillus panophthalmitis complicating treatment of pterygium. Cornea 7:285, 1988. 15. Altman, A. ]., Cohen, E. J., Berger, S. T., and
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Mondino, B. J.: Scleritis and Streptococcus pneumoniae. Cornea 10:341, 1991. 16. Deodati, F., Bec, P., Labro, J. B., and Barrioulet, Y.: Sclerite syphilitique. Aspect clinique et angiographique. Bull. Soc. Ophtalmol. Fr. 71:63, 1971. 17. Wilhelmus, K. R., and Yokoyama, C. M.: Syph ilitic episcleritis and scleritis. Am. J. Ophthalmol. 104:595, 1987. 18. Donahue, H. C : Ophthalmologic experience in a tuberculosis sanatorium. Am. J. Ophthalmol. 64:742, 1967. 19. Bloomfield, S. E., Mondino, B., and Gray, G. F.: Scierai tuberculosis. Arch. Ophthalmol. 94:954, 1976. 20. Nanda, M., Pflugfelder, S. C , and Holland, S.: Mycobacterium tuberculosis scleritis. Am. J. Ophthal mol. 108:736, 1989. 21. Schuman, J. S., Weinberg, R. S., Ferry, A. P., and Guerry, R. K.: Toxoplasmic scleritis. Ophthal mology 95:1399, 1988. 22. Watson, P. G., and Hayreh, S. S.: Scleritis and episcleritis. Br. J. Ophthalmol. 60:163, 1976. 23. Rao, N. A., Marak, G. E., and Hidayat, A. A.: Necrotizing scleritis. A clinico-pathologic study of 41 cases. Ophthalmology 92:1542, 1985. 24. Weinberg, R. S.: Endogenous bacterial and
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fungal infections of the retina and choroid. In Tab bara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, pp. 501-503. 25. Raistrick, E. R., and Dean Hart, J. C. D.: Ocu lar toxocariasis in adults. Br. J. Ophthalmol. 60:365, 1976. 26. Shields, J. A.: Ocular toxocariasis. A review. Surv. Ophthalmol. 28:361, 1984. 27. Tabbara, K. F.: Other parasitic infections. In Tabbara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, pp. 682-688. 28. Jackson, W. B.: Infections of the sclera. In Tab bara, K. F., and Hyndiuk, R. A. (eds.): Infections of the Eye. Boston, Little, Brown, and Company, 1986, p. 481. 29. Duke-Elder, S., and Leigh, A. G.: Diseases of the Outer Eye. Cornea and Sclera. In Duke-Elder, S. (ed.): Systems of Ophthalmology, vol. 8, pt. 2. Lon don, Henry Kimpton, 1965, pp. 1024-1033. 30. Stenson, S., Brookner, A., and Rosenthal, S.: Bilateral endogenous necrotizing scleritis due to Aspergillus oryzae. Ann. Ophthalmol. 14:67, 1982. 31. Womack, L. W., and Liesegang, T. J.: Compli cations of herpes zoster ophthalmicus. Arch. Oph thalmol. 101:42, 1983.
