British Journal ofOphthalmology 1992; 76: 694-696

Nocardia choroidal abscess

William B Phillips, Carol L Shields, Jerry A Shields, Ralph C Eagle Jr, Leo Masciulli,David L Yarian

Wills Eye Hospital,Philadelphia, PA, USA

Oncology ServiceW B PhillipsC L ShieldsJ A Shields

Department of PathologyR C Eagle, Jr

Department ofOphthalmology, RobertWood JohnsonUniversity Hospital, NewBrunswick, NJ, USAL MasciulliD L YarianCorrespondence to:Jerry A Shields, MD,Director, Oncology Service,Wills Eye Hospital, Ninth andWalnut Streets, Philadelphia,Pennsylvania 19107, USA.Accepted for publication9 June 1992

AbstractNocardia is a Gram positive, aerobic,filamentous branching micro-organism thatrarely causes human infection. When infectiondoes occur it usually takes the form of asubcutaneous abscess or a pneumonia-likeillness. We describe a case of a patient withchronic lymphocytic leukaemia who developedpainless loss of vision in the right eye second-ary to a choroidal abscess after a prolongedcourse of treatment on several immuno-suppressive agents. The patient alsocomplained of right shoulder pain that wasunresponsive to conventional therapy, and hadbeen admitted and treated for several episodesof 'pneumonia'. A diagnostic transvitreal fine-needle aspiration biopsy of the ocular lesionwas performed which demonstrated Nocardiaasteroides. This allowed for appropriate anti-biotic therapy to be instituted early in thecourse of the infection and prompted thesystemic work-up which also demonstratedcentral nervous system and arthropic nocardialinfection.(BrJ Ophthalmol 1992; 76: 694-696)

Nocardia is an aerobic, Gram positive, branchingfilamentous micro-organism that is found withubiquity in the soil. Human infection is rare andusually occurs in the form of a subcutaneousabscess or a pneumonia-like illness. Haemato-

;

Figure I Fundus photograph showing submacular choroidal lesion of the right eye withoverlying retinal haemorrhage.

genous dissemination of the organism,particularly in an immunocompromised host,may occur to any organ system and there is apredilection for the central nervous system. ' Wedescribe a patient with chronic lymphocyticleukaemia (CLL) in whom nocardiosis wasinitially diagnosed by a fine-needle aspirationbiopsy of a choroidal abscess.

Case reportA 63-year-old white male presented with a 2week history of painless loss of vision in his righteye. He was diagnosed in 1985 with CLL andhad been controlled by several chemotherapeuticregimens, most recently fludarabine and predni-sone. He did give a history of several episodesof pneumonia that were believed to be bacterial,and responded slowly to antibiotic therapy. Fourweeks before our examination, he developedright shoulder pain that did not respond toindomethacin.On initial ophthalmic examination, his best

corrected visual acuity was 20/400 in the righteye and 20/20 in the left eye. Intraocular pressureswere normal. The left eye was normal. Slit-lampbiomicroscopy of the right eye revealed normalfindings except for cells in the anterior vitreous.Funduscopic examination of the right eyedemonstrated a yellow submacular choroidallesion with overlying intraretinal and subretinalhaemorrhage (Fig 1). Localised retinal thicken-ing and subretinal fluid were noted. There wereno cells in the posterior vitreous.

Ultrasonography of the right eye showed anacoustically hollow choroidal mass with lowinternal reflectivity measuring 3 0 mm in depth.Overlying subretinal fluid and superficialchoroidal infiltration were noted. The lesionblocked choroidal background fluorescence inthe venous phase of fluorescein angiography (Fig2). Mottled areas of increased fluorescencedeveloped within the lesion as the study pro-gressed and there was diffuse staining of thesurrounding retinal vessels. Progressive leakagefrom the lesion, and persistent blockage owing tothe retinal haemorrhage were evident during therecirculation phase (Fig 3).A transvitreal fine-needle aspiration biopsy

was performed by a previously described tech-nique to obtain diagnostic material from thelesion.2 A bent 25 gauge needle was insertedthrough pars plana at 8 o'clock and passed in atransvitreal fashion into the lesion under indirectophthalmoscopic guidance. The needle wasconnected via plastic tubing to a 10 ml syringeand a small amount of diagnostic material wasaspirated into the needle bore. Aspiration wasthen stopped and the needle gently removedfrom the eye. Minimal haemorrhage at thebiopsy site was curtailed with tamponade and

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Nocardia choroidal abscess

Figure 2 Fluoresceinangiogram of the right eye(venous phase) showingblockage ofchoroidalbackground fluorescence bythe lesion.

Figure 3 Fluoresceinangiogram ofthe right eye(recirculation phase)showing progressive leakagefrom the lesion.

balanced salt solution was injected to raise theintraocular pressure to normal. The needle was

then removed from the connector tube andimmediately immersed in saline solution. Thesaline was aspirated through the needle, flushingthe material into the syringe. All materialobtained was then submitted for microbial andcytological examination which showed acute andchronic inflammatory cells and red blood cells.No organisms or leukaemic cells were seen. The

Gram stain showed Gram positive, branching,filamentous organisms consistent with Nocardia.Nocardia asteroides was isolated in a microbio-logical culture. The organism was sensitive toamikacin, cefotaxime, erythromycin, trimetho-prim, and sulphamethoxazole. No otherorganisms were identified.Therapy with parenteral trimethoprim/

sulphamethoxazole was instituted and the patientwas evaluated for systemic nocardiosis.Computed tomography (CT) revealed approxi-mately 35 small presumed nocardial abscesses inthe brain. It should be noted that at this time thepatient was not experiencing any symptoms thatwere believed to be related to CNS nocardiosis.Additionally, synovial fluid aspirated from thepatient's painful right shoulder demonstratedorganisms compatible with Nocardia asteroides.The systemic nocardiosis responded somewhatduring a 1 month period of intensive intravenoustreatment. A repeat CT scan of the brainapproximately 4 months later demonstratedresolution of the CNS lesions, and the rightshoulder pain had abated. The choroidal abscessappeared to enlarge somewhat over the following4 months and the patient was subsequently givenintravitreal injections of amikacin (400 [tg)and cephazolin (Ancef, USA) (2-25 mg). Overthe next 3 months, the abscess became anelevated, subretinal fibrotic mass with a resultantvisual acuity of hand movement in the right eye.Visual acuity in the left eye remained 20/20, witha normal ocular examination. Currently, thepatient is maintained on oral co-trimoxazole andthe visual acuity is unchanged.

DiscussionHistorically, nocardial infections in humans arevery rare and often self-limited. Their frequencyand severity are increasing, however, asimmunosuppressive and chemotherapeuticagents are used more frequently.3 The use ofcyclophosphamide and steroids in combinationhas been shown experimentally to increasesusceptibility to nocardial infection.'

Nocardia asteroides, a member of the orderActinomycetales, is a slow growing, Grampositive, variably acid-fast, filamentous aerobicorganism that inhabits the soil.4 The organismgrows readily over a wide temperature range andon relatively simple media. Nocardia asteroidesand Nocardia brasiliensis are the two mostcommon species that cause morbidity in humanswithN asteroides accounting for about 90% of thecases. The infection is commonly acquired viathe pulmonary route by inhalation of theorganism, or subcutaneously by direct contami-nation of an open skin wound. The pulmonarylesions tend to simulate tuberculosis or histo-plasmosis. Approximately 50% of patients withpulmonary nocardiosis have haematogenousdissemination, particularly to the brain.Currently, trimethoprim-sulphamethoxazole isthe drug of choice for treating nocardiosis. Incases of antibiotic resistance or allergy, eitheramikacin, minocycline, or ampicillin anderythromycin in combination have been found tobe effective. Nocardia also shows susceptibilityto some of the second and third generation

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Phillips, Shields, Shields, Eaglejr, Masciulli, Yarian

cephalosporins. Although our patient's CNS andarthropic infection appeared to respond totreatment, the ocular lesion demonstrated pro-gression. Antibiotic resistance is unlikely sincethe brain abscesses and right shoulder painresolved during treatment. It is possible thatalthough both trimethoprim and sulpha-methoxazole serum levels were in the therapeuticrange, these levels may be insufficient to eradicatean intraocular infection. To our knowledgetherapeutic levels of trimethoprim and sulpha-methoxazole have not been determined forintraocular nocardial infections, nor have serumlevels been correlated with aqueous or vitreallevels.

In the case presented, a patient with knownCLL on immunosuppressive therapy developeddecreased vision in his right eye. Ophthalmicexamination disclosed a submacular choroidalabscess. Previously, the patient had beenhospitalised for numerous pulmonary infectionsand more recently developed right shoulderpain. Though not proved, it is probable thatNocardia was a causative agent in some of thesepulmonary infections. We speculate that haema-togenous dissemination from the lungs resulted

in nocardial infection in the eye, shoulder, andCNS.

In immunocompromised patients withchorioretinal infiltrative lesions, opportunisticorganisms are frequently the causative agents. Inthis, and a previously described case,5 trans-vitreal fine-needle aspiration biopsy of the lesionled to early, accurate identification of theorganism. Appropriate antibiotic therapy andsystemic work-up were then implemented earlyin the course of the infection. This is particularlyimportant as a delay in appropriate therapy isassociated with increased morbidity andmortality.

The investigation was supported in part by the Ocular OncologyFund, Wills Eye Hospital and the EyeTumor Research FoundationInc, Gladwyne, PA, USA.

1 Bullock JD. Endogenous ocular nocardiosis: a clinical andexperimental study. TransAm Ophthalmol Soc 1983; 81: 451-531.

2 Shields JA, Shields CL. Intraocular tumors: a text and atlas.Philadelphia: Saunders, 1992: 20-3.

3 Jampol LM, Stauch BS, Albert DM. Intraocular nocardiosis.AmJ Ophthalmol 1973; 76: 568-73.

4 Davis BD, Dulbecco R, Eisen HN, et al. Microbiology, 3rd ed.Philadelphia: Harper & Row, 1980: 744-9.

5 Gregor RJ, Chong CA, Augsburger JA, et al. EndogenousNocardia asteroides subretinal abscess diagnosed by trans-vitreal fine needle aspiration biopsy. Retina 1989; 9: 118-21.

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