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Arch Ophthalmol. 2002;120:210-213.

Nocardia asteroides, a Gram-positive, aerobic, soil-borne bacterium, is a cause of opportunistic infections in immunocompromised patients, particularly those with lymphoreticular neoplasms, long-term pulmonary disorders, and long-term steroid use. The organism is usually inhaled and may cause localized or disseminated infections. A predilection for its spread to the brain and soft tissues has been noted. Suppurative necrosis and abscess formation is the pathologic hallmark. Nocardia is distinguished by beaded, branching, filamentous growth in purulent exudate and tissue sections.

Ocular involvement by Nocardia is very rare, with approximately 30 cases of intraocular nocardial infection reported in the literature.^1-4 Optimal therapeutic regimens are not established. Only 2 reports detail experiences with intravitreal antibiotics.⁵ We report our experience with a case of endogenous N asteroides endophthalmitis treated with vitrectomy and intraocular and systemic antibiotics, and for which a diagnostic subretinal biopsy was performed.

Report of a Case
A 69-year old man was admitted to our hospital with pleuritic chest pain, chronic fatigue, weight loss, and a left upper lobe lung mass on computed tomography, which was judged to be a malignant or infectious process. The patient had glomerulonephritis with renal failure and had received oral prednisone for 16 months. Ocular history was unremarkable.

During admission, the patient reported having 2 days of floaters in the right eye. No pain or photophobia was present. Examination disclosed visual acuity of 20/30 OD and 20/20 OS. Pupils, visual fields to count fingers, color-plate test results, and tensions were normal. Slitlamp examination disclosed mild cataracts in both eyes. Ophthalmoscopy of the right eye disclosed 2+ vitritis and an elevated mass 3 disc diameters in size inferotemporal to the fovea within the vascular arcades (Figure 1). The lesion was yellowish with hemorrhages on the surface. The disc was unremarkable. Ophthalmoscopy findings of the left eye were unremarkable.

View larger version (17K): [in this window] [in a new window] Figure 1. A, Ophthalmic appearance of the optic nerve head and subretinal abscess in the temporal area of the macula. B, Yellowish appearance of the subretinal abscess with overlying retinal hemorrhages. Moderate vitritis was present.

The following day, visual acuity declined to 20/100 OD and 2+ anterior chamber cell and 3+ vitritis were present. Vitreous tap was performed and samples were sent for bacterial and fungal cultures and mycobacterial stains. A tuberculin skin test was performed. Serologic tests for herpes simplex and varicella zoster viruses, cytomegalovirus, and syphilis were performed. The patient was treated with 5 µg of intravitreal amphoterocin B and intravenous amphoterocin B for presumptive fungal endophthalmitis. The oral prednisone was tapered.

The patient was observed for 1 week, with no improvement. Bronchoscopic and transthoracic needle biopsies of the lung lesion were attempted but histopathologic test results disclosed inflammation only, with no tumor or organisms present. A wedge resection of the lung lesion was subsequently performed.

One week after initial intravitreal injection, visual acuity had declined to hand motions OD. A relative afferent papillary defect was present in the right eye. The ocular lesion now appeared to involved much of the macula and optic disc, although it was difficult to view because of dense vitritis. All cultures and serologic test results were negative at this time. A second intravitreal injection of 5 µg of amphoterocin B was administered.

Pars plana vitrectomy with retinal and subretinal biopsy were performed 10 days after the initial ocular examination. Intraoperatively, a large yellowish mass was present inferotemporally and extended to within 1 disc diameter of the fovea. Subretinal fluid was present throughout the macula. Neuroretinitis was present and extended from the optic disc along the superior and inferior temporal arcades. During biopsy, the subretinal tissue was noted to be extremely firm in consistency. Intravitreal vancomycin (1 mg) and ceftazidime (2 mg) were injected at the end of the procedure followed by fluid-gas exchange.

Eleven days after initial ocular presentation, examination of the lung specimen disclosed filamentous organisms. Thirteen days after presentation, the culture of the lung tissue was positive for N asteroides (ie, at 8 days of growth). The patient began taking oral trimethoprim-sulfamethoxazole. Based on sensitivity data, the eye was injected intravitreally with 25 µg of imipenem and 200 µg of amikacin (doses were adjusted downward to account for the 50% air bubble in the vitreous). Cultures of the vitrectomy specimen became positive at 4 days of growth and organisms consistent with Nocardia species were noted on transmission electron microscopy of the subretinal biopsy.

Postoperatively, no view of the posterior segment was possible. Echography performed 1 week after surgery disclosed an extensive shallow retinal detachment with enlargement of the lesion. Surgical repair was considered but was not performed due to the patient's anesthesia risk.

A 4-mm-diameter ring-enhancing lesion of the left temporal lobe was noted on a brain magnetic resonance imaging scan, which was considered to be a small abscess (Figure 2). The lesion remained stable during treatment. The patient was discharged 3 weeks after admission due to improvement in his systemic condition. Long-term oral trimethoprim-sulfamethoxazole was prescribed. A 2-week course of outpatient intravenous therapy with ceftriaxone sodium was administered for the ocular infection. Six months after the onset of the condition, the results of a repeated magnetic resonance image scan of the brain disclosed resolution of the temporal lobe lesion. However, the patient's visual acuity deteriorated to no light perception, the eye became phthisical, and it was enucleated 7 months after the onset of the ocular condition.

View larger version (60K): [in this window] [in a new window] Figure 2. Axial magnetic resonance imaging scan of the brain disclosed a 4-mm-diameter ring-enhancing lesion (arrow) of the left temporal lobe that was judged to be an abscess. Moderate enhancement of the sclera of the right globe with associated minimal enhancement of periorbital tissues was present.

Histopathologic examination results of the vitreous specimens disclosed an intense polymorphonuclear leukocyte infiltrate. Light and electron microscopic evaluation of the retinal biopsy disclosed fibrinous material and a dense infiltrate of polymorphonuclear leukocytes and mononuclear inflammatory cells. No organisms were identified. Electron microscopic study of the subretinal biopsy disclosed numerous filamentous, septated organisms that measured 1.1 µm in diameter (Figure 3). Histopathologic examination of the lung biopsy specimen revealed bronchopneumonia with occasional clusters of filamentous organisms with the silver stain (Figure 4). Examination of the enucleated eye disclosed iris neovascularization, cyclitic membrane, detachment of the retina with extensive subretinal proliferation, a serosanguinous ciliochoroidal effusion, rare foci of lymphocytes in the choroid, and no microbial organisms.

View larger version (175K): [in this window] [in a new window] Figure 3. Ultrastructural appearance of septated filamentous organisms that measured 1.1 µm in diameter in the subretinal biopsy (A, original magnification x8100; B, x15 000; C, x60 000).

View larger version (59K): [in this window] [in a new window] Figure 4. Filamentous organisms in the lung biopsy specimen (A and B, Gomori methanamine silver; original magnification x1000).

Comment
Endogenous N asteroides endophthalmitis is associated with dismal outcomes, with many eyes progressing to blindness despite treatment. The primary site of infection is most often in the lung. Patients may have features of anterior or posterior uveitis. Symptoms include floaters, decreased vision, pain, and photophobia. Chorioretinitis with subretinal abscess formation is the hallmark of endogenous nocardial endophthalmitis.⁶ Exudative retinal detachment may occur. Typically, organisms are located under the retinal pigment epithelium or in the subretinal space and may proliferate along the Bruch membrane.⁶

Nocardia infections may be difficult to diagnose. Organisms can be identified on Gram, acid-fast, and Gomori methenamine silver stains. Nocardia organisms grow readily on most nonselective media and typical colonies are usually seen after 3 to 5 days. Cultures and smears are positive in only one third of cases. Retinal and subretinal biopsies were performed in this case because of diagnostic uncertainty. Electron microscopic examination of the subretinal biopsy was successful in demonstrating organisms.

The treatment of ocular nocardial infection has been met with limited success, although favorable outcomes are common for infections at nonocular sites. The role of vitrectomy in nocardial endophthalmitis is uncertain. We injected amikacin and imipenem intravitreally in our patient. Although toxicity data are limited for imipenem,^7-8 it displays comparable efficacy to intravitreal vancomycin in experimental Bacillus cereus endophthalmitis,⁹ and to amikacin in experimental Pseudomonas aeruginosa endophthalmitis.¹⁰ We chose to administer intravitreal imipenem in light of these data, known nocardial sensitivity and synergy data, and the patient's deteriorating ocular condition. A course of intravenous ceftriaxone was also added for the above reasons. Despite these measures, phthisis ensued in our patient.

Sulfonamides remain the antibiotic of choice for Nocardia elsewhere in the body. Trimethoprim-sulfamethoxazole is the preferred formulation by most clinicians despite increased myelotoxicity with this combination. In vitro synergistic activity has been demonstrated against most isolates.¹¹ The variable and chronic course of nocardiosis necessitates long treatment durations (6-12 months). Alternative regimens are largely based on in vitro susceptibilities and efficacy in animal models, and include amikacin and imipenem¹² and other combinations.^13-14

AUTHOR INFORMATION
Supported in part by the FA Hadley Travelling Scholarship, the University of Western Australia, Perth, Australia, and the Independent Order of Odd Fellows, Winston-Salem, NC.

Eugene W. M. Ng, MD; Ingrid E. Zimmer-Galler, MD; W. Richard Green, MD
Baltimore, Md

Corresponding author: W. Richard Green, MD, Eye Pathology Laboratory, The Johns Hopkins Hospital, Maumenee 427, 600 N Wolfe St, Baltimore, MD 21287.

REFERENCES
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SECTION EDITOR: W. RICHARD GREEN, MD

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