2013 Ocular Immunology & Inflammation, Early Online, 1–4, 2013 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.810276 ORIGINAL ARTICLE Intraocular Cysts of Toxoplasma gondii in Patients with Necrotizing Retinitis following Periocular/Intraocular Triamcinolone Injection Raje Nijhawan, MD 1 , Reema Bansal, MD 2 , Nalini Gupta, MD 1 , Nikhil Beke, MD 2 , Pandurang Kulkarni, MD 2 , and Amod Gupta, MD 2 1 Department of Cytology & Gynecological Pathology and 2 Department of Ophthalmology, Post Graduate Institute of Medical Education & Research, Chandigarh, India ABSTRACT Purpose: To report the detection of Toxoplasma gondii cysts in intraocular aspirates of patients with necrotizing retinitis following periocular/intraocular corticosteroid injection. Design: Case report. Methods: Two patients (2 eyes) with widespread necrotizing retinitis in a steroid-exposed eye posed a diagnostic challenge and underwent pars plana vitrectomy (PPV). Intraocular samples (vitreous fluid, retinal tissue, and subretinal aspirate in case 1, and vitreous fluid in case 2) were subjected to cytological examination. Results: The subretinal aspirate (case 1) revealed encysted bradyzoites of Toxoplasma gondii. Vitreous fluid (case 2) tested positive for anti-toxoplasma antibodies and the smear showed encysted forms of Toxoplasma gondii on cytology. Conclusion: Toxoplasma gondii cysts were detected in eyes with necrotizing retinitis that developed secondary to injudicious use of corticosteroids. Keywords: Corticosteroids, cytology, intraocular, subretinal, Toxoplasma gondii, vitreous Toxoplasma gondii is an intracellular parasite with a predilection for multiple tissues, including the eye. Ocular toxoplasmosis characteristically displays focal necrotizing retinitis, occurring from the activation of cysts in the retina. Within the necrotic retina, cysts of Toxoplasma gondii can be found. 1 Yet, direct confirm- ation by demonstrating organisms in ocular samples is extremely difficult. 2 Its diagnosis is usually clinical, confirmed by presence of anti-toxoplasma antibodies. Direct evidence from vitreous fluid is increasingly becoming possible by polymerase chain reaction (PCR) and, rarely, by cytology. 3 More invasive ret- inal/subretinal biopsies are performed following a failure to confirm a diagnosis. 4 Diagnosis of ocular toxoplasmosis presents a chal- lenge in immunocompromised individuals when it causes diffuse necrotizing retinitis, mimicking viral retinitis. We report two patients who developed widespread necrotizing retinitis following exposure to corticosteroids, and did not respond to empiric therapy for viral retinitis. Cytological examination revealed the presence of Toxoplasma gondii cysts in intraocular samples. CASE 1 A 71-year-old male presented to us with right eye panuveitis, having received elsewhere a posterior subtenon injection of triamcinolone acetonide 9 months before. The best-corrected visual acuity (BCVA) was 6/60 and 6/6 in the right and left eyes, respectively. The intraocular pressure (IOP) was 30 and 13mm Hg in the right and left eyes, respectively. Correspondence: Dr. Amod Gupta, Professor & Head, Advanced Eye Centre, Dean, Post Graduate Institute of Medical Education & Research, Chandigarh 160 012, India. E-mail: [email protected]Received 24 July 2012; revised 4 October 2012; accepted 4 October 2012; published online 22 July 2013 1 Ocul Immunol Inflamm Downloaded from informahealthcare.com by University Library Utrecht on 09/03/13 For personal use only.
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2013
Ocular Immunology & Inflammation, Early Online, 1–4, 2013! Informa Healthcare USA, Inc.
ISSN: 0927-3948 print / 1744-5078 online
DOI: 10.3109/09273948.2013.810276
ORIGINAL ARTICLE
Intraocular Cysts of Toxoplasma gondii in Patients withNecrotizing Retinitis following Periocular/Intraocular
Triamcinolone Injection
Raje Nijhawan, MD1, Reema Bansal, MD
2, Nalini Gupta, MD1, Nikhil Beke, MD
2,Pandurang Kulkarni, MD
2, and Amod Gupta, MD2
1Department of Cytology & Gynecological Pathology and 2Department of Ophthalmology, Post GraduateInstitute of Medical Education & Research, Chandigarh, India
ABSTRACT
Purpose: To report the detection of Toxoplasma gondii cysts in intraocular aspirates of patients with necrotizingretinitis following periocular/intraocular corticosteroid injection.
Design: Case report.
Methods: Two patients (2 eyes) with widespread necrotizing retinitis in a steroid-exposed eye posed a diagnosticchallenge and underwent pars plana vitrectomy (PPV). Intraocular samples (vitreous fluid, retinal tissue, andsubretinal aspirate in case 1, and vitreous fluid in case 2) were subjected to cytological examination.
Results: The subretinal aspirate (case 1) revealed encysted bradyzoites of Toxoplasma gondii. Vitreous fluid (case2) tested positive for anti-toxoplasma antibodies and the smear showed encysted forms of Toxoplasma gondii oncytology.
Conclusion: Toxoplasma gondii cysts were detected in eyes with necrotizing retinitis that developed secondary toinjudicious use of corticosteroids.
Toxoplasma gondii is an intracellular parasite with apredilection for multiple tissues, including the eye.Ocular toxoplasmosis characteristically displays focalnecrotizing retinitis, occurring from the activation ofcysts in the retina. Within the necrotic retina, cysts ofToxoplasma gondii can be found.1 Yet, direct confirm-ation by demonstrating organisms in ocular samplesis extremely difficult.2 Its diagnosis is usually clinical,confirmed by presence of anti-toxoplasma antibodies.Direct evidence from vitreous fluid is increasinglybecoming possible by polymerase chain reaction(PCR) and, rarely, by cytology.3 More invasive ret-inal/subretinal biopsies are performed following afailure to confirm a diagnosis.4
Diagnosis of ocular toxoplasmosis presents a chal-lenge in immunocompromised individuals when itcauses diffuse necrotizing retinitis, mimicking viral
retinitis. We report two patients who developedwidespread necrotizing retinitis following exposureto corticosteroids, and did not respond to empirictherapy for viral retinitis. Cytological examinationrevealed the presence of Toxoplasma gondii cysts inintraocular samples.
CASE 1
A 71-year-old male presented to us with right eyepanuveitis, having received elsewhere a posteriorsubtenon injection of triamcinolone acetonide 9months before. The best-corrected visual acuity(BCVA) was 6/60 and 6/6 in the right and left eyes,respectively. The intraocular pressure (IOP) was 30and 13 mm Hg in the right and left eyes, respectively.
Correspondence: Dr. Amod Gupta, Professor & Head, Advanced Eye Centre, Dean, Post Graduate Institute of Medical Education & Research,Chandigarh 160 012, India. E-mail: [email protected]
Received 24 July 2012; revised 4 October 2012; accepted 4 October 2012; published online 22 July 2013
The right eye biomicroscopy showed þþ flare and þcells in the anterior chamber, posterior synechiae, andsignificant vitritis. Fundus examination revealed apatch of retinitis in the macula with scattered retinalhemorrhages (Figure 1). An extensive area of retinalatrophy was noted inferotemporal to the macula. Theleft eye was normal. He was seronegative for humanimmunodeficiency virus infection. The clinical pictureand a positive serum IgG for HSV was suggestive ofacute retinal necrosis and was unsuccessfully treatedwith acyclovir and oral corticosteroid therapy. In viewof the persistent inflammation at 6 months, heunderwent pars plana vitrectomy (PPV). Vitreousfluid revealed no organisms or malignant cells oncytology. At 10 months, retinal tissue and subretinalaspirate were obtained during repeat PPV for cytol-ogy, followed by silicon oil tamponade. Retinal tissuewas normal but the subretinal aspirate revealed
encysted bradyzoites, structures consistent with theencysted bradyzoites of Toxoplasma gondii cysts(Figure 2). After 3 days of antitoxoplasma drugs,BCVA was counting fingers, IOP 10 mmHg, anteriorchamber showed cells þ, flare þ, and retina wasattached (Figure 3). The patient was lost to follow upthereafter.
CASE 2
A 29-year-old female presented with decreased visionin the right eye since 8 months. She had receivedintravitreal triamcinolone acetonide, oral corticoster-oids, and antitubercular therapy elsewhere. TheBCVA was counting fingers and 6/6 in the right andleft eyes, respectively. The IOP was 15 and 13 mmHgin the right and left eyes, respectively. The right eyeanterior segment examination was unremarkable.Fundus examination revealed a widespread areaof necrotizing retinitis in the posterior pole with ahealed choroiditis scar along inferotemporal arcade(Figure 4). The left eye was normal. Serum anti-toxoplasma IgG antibodies were positive. Vitreousaspirate from diagnostic PPV was positive for anti-toxoplasma IgG and IgM antibodies. Vitreous cytol-ogy smear showed structures consistent withToxoplasma gondii cysts (Figure 5). One month afterinitiating antitoxoplasma therapy, BCVA was countingfingers and lesions were resolving (Figure 6).
DISCUSSION
There are occasional reports of demonstration oftoxoplasma organisms in tissue biopsies/cytology,3,4,
necropsy material,5 or enucleated eyes.6,7 Within the
FIGURE 3. Fundus photograph (case 1) 3 days after surgery(pars plana vitrectomyþpartial retinectomyþ endolaser photo-coagulationþ silicon oil tamponade) showing attached retina ina silicon-oil filled eye.
FIGURE 1. Fundus photograph (a) of right eye of the patient(case 1) at initial visit with visual acuity 6/60. There wassignificant vitritis with a yellowish placoid lesion in posteriorpole and retinal hemorrhages in periphery.
FIGURE 2. Subretinal aspirate (case 1) showing structuresconsistent with Toxoplasma gondii cysts with numerous brady-zoites, and a pigment-laden macrophage (May-GrumwaldGiemsa, �1000).
2 R. Nijhawan et al.
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eye, the parasite has an affinity for retina, particularlythe posterior pole. Leucocyte taxis and direct inter-action with the vascular endothelium have beenproposed mechanisms. An in vitro study has demon-strated that tachyzoites are capable of independentmigration across human vascular endothelium.8
Our patients had been extensively treated withlocal (periocular/intravitreal) and oral corticosteroidsthat triggered widespread retinal necrosis facilitatingthe growth and migration of toxoplasma parasitesleading to their subsequent detection on cytology ofsubretinal and vitreous aspirates. In the first case,failure to detect them in the vitreous aspirate or retinaltissue highlights the difficulty in detecting theseorganisms on cytology of intraocular samples. Theparasite may harbor in selected areas of the eye, andmay not be diffusely present in the uvea and retina.Their isolation from the subretinal aspirate in thiscase, as also reported by Adan et al. recently,4 may
suggest their preferential colonization in the deeperlayers in an immunocompromised state. Adan et al.reported an atypical toxoplasmic retinochoroiditis inan elderly male with post-transfusional hepatitis Cwho also received high-dose systemic corticosteroids.4
The vitreous aspirate did not reveal toxoplasma inPCR or on cytology. The subretinal aspirate revealedtoxoplasma organisms on cytology. Their isolationfrom the vitreous aspirate (as in our second case, andalso reported previously3,7) may suggest a moreextensive necrosis of the retina, releasing the cystsinto the vitreous cavity.9
While PCR is an easier technique and preferred incertain infectious uveitis (viral) over the Goldmann-Witmer coefficient (GWC), which detects intraocularantibody production, the latter has shown superiorresults in diagnosing ocular toxoplasmosis whencompared to PCR of aqueous humor.10 The slowrelease of Toxoplasma gondii tachyzoites from the cystsinto the ocular fluid may explain the absence ofpositive PCR results in early stages.10 Further, theirsubsequent accumulation within the vitreous cavitymay explain their detection on cytological examin-ation, which is usually performed much later follow-ing an initial negative vitreous biopsy report of PCR.In an immunocompromised individual, PCR seemspreferable to GWC analysis since the antibody pro-duction is unpredictable. However, in case of oculartoxoplasmosis, GWC analysis has contributed to itsdiagnosis considerably more than PCR in immuno-suppressed patients.11
Due to the atypical clinical presentations, an initialnoncontributory vitreous biopsy report, a poorresponse to therapy, and a high clinical suspicion oftoxoplasmosis in an immunocompromised eye, weresorted to more invasive tests, such as retinal orsubretinal biopsy. In our cases, the long period ofinadequate treatment before definite cytologicalexamination might have contributed to the diagnosticyield of these tests. The cytopathologist needs to be
FIGURE 4. Fundus photograph of right eye (case 2) shows awidespread necrotizing retinitis with a healed choroiditis scaralong the lower temporal arcade.
FIGURE 6. Fundus photograph (case 2) at 1 month follow-upshowing healing lesions after anti-toxoplasma therapy wasinitiated.
FIGURE 5. Vitreous smear (case 2) showing structures consist-ent with Toxoplasma gondii cysts in the main picture and in theinset (May-Grumwald Giemsa, �1000).
Cysts of Toxoplasma Gondii in Eye 3
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vigilant for a meticulous search for organisms in thesesamples. With advancement in sampling techniques,it may be possible to demonstrate the protozoan in agreater proportion of ocular samples sent to thecytology laboratory.
Differentiation of infectious from noninfectiousetiology is of utmost importance in the treatment ofuveitis as they differ largely in terms of treatment andprognosis. Inadvertent use of corticosteroids shouldbe avoided in an inflamed eye, particularly in theabsence of a definitive diagnosis.
DECLARATION OF INTEREST
The authors report no conflicts of interest. Theauthors alone are responsible for the content andwriting of the paper.
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