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.
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.
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
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.
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.
Ultrastructural appearance of
septated filamentous organisms that measured 1.1 µm in diameter in the
subretinal biopsy (A, original magnification ×8100; B, ×15 000;
C, ×60 000).
Filamentous organisms in the lung
biopsy specimen (A and B, Gomori methanamine silver; original magnification
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
Supported in part by the FA Hadley Travelling Scholarship, the University
of Western Australia, Perth, Australia, and the Independent Order of Odd Fellows,
Corresponding author: W. Richard Green, MD, Eye Pathology Laboratory,
The Johns Hopkins Hospital, Maumenee 427, 600 N Wolfe St, Baltimore, MD 21287.
Ng EWM, Zimmer-Galler IE, Green WR. Endogenous Nocardia asteroides Endophthalmitis. Arch Ophthalmol. 2002;120(2):210-213. doi: