MIGRATING BEHAVIOR OF PRESUMED TOXOCARA PRESENTING AS PUNCTATE INNER CHOROIDOPATHY, IDIOPATHIC CHOROIDAL NEOVASCULARIZATION, AND DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS Eduardo C. De Souza, MD, PhD,* Eduardo Raskin, MD,† Leonardo Castro, MD,* Lilia Muralha, MD,‡ Osias Souza, MD,† Rafael Pena, MD‡
Purpose: To document the intraretinal migration of presumed toxocara larvae mimicking punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis. Methods: Sequential color photographs, fluorescein angiograms, and optical coherence tomography were performed in three unrelated adult patients with presumed ocular toxocariasis. Results: Characteristic fundoscopic manifestations simulating punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis were reported in these patients, respectively. Conclusion: Presumed toxocara larvae must be included as a potential cause of different inflammatory diseases as a result of its migration through the retinal layers. RETINAL CASES & BRIEF REPORTS 6:430–434, 2012
larvae travel throughout the small animals’ intestines where the adult worms produce eggs. Several thousand eggs are produced per day and are shed in an infected animal’s feces into the soil where they can live dormant for several months to years.1 Similarly, in humans, the eggs hatch in the intestines and the larvae penetrate the intestinal wall entering the circulation. As an intermediate host for Toxocara spp., the larvae cannot develop into adult worms or multiply in an infected human. The disease process is noticed only when an immunologic reaction is activated in the host.1 For example, when second-stage and third-stage larvae enter the eye through the blood circulation, they typically tend to migrate from the choroidal vessels, across the retina, toward the vitreous cavity. This migrating behavior of toxocara can be associated with an eosinophilic type of granulomatous response in these ocular tissues.3 We believe to have examined three unrelated young Brazilian patients with this
From the *Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil; †Department of Ophthalmology, Universidade de Campinas; and ‡Department of Ophthalmology, Hospital de Olhos Niterói, Niteroi, Brazil.
T
oxocara canis and Toxocara cati are nematodes known to cause toxocariasis in dogs and cats, as well as ocular toxocariasis in humans.1,2 Both nematodes are accidentally contracted in humans by eating eggs in dirt and by contacting an infected animal.1 Toxocara spp., a roundworm parasite, infects puppies and kittens that ingest the eggs or larvae. The Presented as a Scientific Poster at the Retinal Congress, New York, NY, September 30-October 4, 2009. The authors declare no conflict of interest. Reprint requests: Eduardo C. De Souza, MD, PhD, Department of Ophthalmology, Universidade Federal de São Paulo (UNIFESP), Rua Mato Grosso 306 4th 411, São Paulo, 01239 040 Brazil; e-mail: [email protected]
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mechanism of ocular toxocariais mimicking punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis (DUSN). Case Reports Case 1 A 23-year-old healthy woman presented with reduced central vision and metamorphopsia in the right eye. She was initially diagnosed with choroidal neovascularization (CNV) secondary to punctate inner choroidopathy. Visual acuity was 20/40 with −1.00
431 (−1.00 · 75), and there was no inflammatory cells in the vitreous. The left eye was normal. Biomicroscopy showed a 1DD yellowish elevated and hemorrhagic lesion superior nasally to the macula in the right eye. Multiple white punctate lesions were seen surrounding the macula temporally (Figure 1A). Fluorescein angiography confirmed the apparent classic CNV aspect of the hemorrhagic lesion and staining of the focal lesions and optic nerve (Figure 1C). Corresponding to the hemorrhagic lesion, optical coherence tomography revealed a protruded granulomatous lesion above the retinal pigment epithelium (RPE) and under the external limitant membrane associated with a shallow retinal detachment extending to the center of the macula (Figure 1B). Over the subsequent days, there was progression of the surrounding subretinal fluid associated with exudates in the macula (Figure 1D) and extension of the
Fig. 1. Case 1. A, Color photograph of the right eye at presentation shows a yellowish hemorrhagic lesion superior nasally to the macula (black arrow). Multiple white punctate lesions were seen surrounding the macula temporally (white arrow). B, An optical coherence tomographic line through the lesion revealed a hyperreflective granulomatous lesion above the RPE and under the external limiting membrane. C, Fluorescein angiogram of the lesion demonstrating features of classic CNV and staining of the focal lesions and optic nerve. D, Note the presence of subretinal fluid and exudates in the macula 1 week after observation. E, A corresponding OCT examination demonstrated extension of the granulomatous lesion to inner portions of the retina. F, Two weeks after treatment, the lesion regressed and a small , translucent, pearl-like structure was observed in the surface of the retina (black arrow). G, A corresponding OCT examination confirmed a further superficial extension of the hyperreflective granulomatous lesion. H, Color photograph showing shrinkage and consolidation of the granulomatous lesion after 1 year of follow-up.
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tomographic granuloma to inner portions of the retina (Figure 1E). A diagnosis of presumed toxocariasis was made and reinforced by a history of recent exposure to kittens and positive immunoglobulin G serologic antibody titer by enzyme-linked immunosorbent assay (ELISA) (88). She was given a 10-day course of Albendazole (400 mg) and oral steroid (20 mg). The serous retinal detachment gradually decreased and vision improved to 20/25. Surprisingly, in the area corresponding to the previous CNV, a small translucent “pearl-like” structure was observed emerging in the superficial layers of the retina (Figure 1, F and G). During the subsequent weeks, there was a progressive shrinkage and consolidation of the granulomatous lesion in that eye (Figure 1H). Visual acuity remained 20/20 without distortion.
Case 2 A 13-year-old boy presented with loss of central vision in the left eye for 3 months. Except for direct contact with cats, the patient’s medical history was unremarkable. He was referred with the diagnosis of idiopathic CNV in his left eye. Visual acuity was 20/80, and there were no inflammatory cells in the vitreous. The right eye was normal. Biomicroscopy showed a whitish yellow mass beneath the macula associated with subretinal fluid and exudates in the left eye. Outside the macula, a small whitish calcified lesion and focal areas of hyperpigmentation were seen superiorly to the disk in this eye (Figure 2A). Angiography revealed a hypofluorescent rim surrounding the CNV-like hyperfluorescent lesion in the macula, indicating the envelopment of the CNV by the RPE (Figure 2D). An optical coherence tomography line through the active macular lesion revealed a highly reflective granulomalike lesion protruding above the RPE and surrounded by subretinal fluid (Figure 2C). Similar findings without subretinal fluid were found for the hyperreflective, calcified, extramacular lesion (Figure 2B). A diagnosis of presumed toxocariasis was mainly
based on the granulomatous aspect of these lesions in this case (positive immunoglobulin G–ELISA of 116). The patient was given a 10-day course of albendazole (400 mg) and oral steroid (20 mg). Regression of the macular granuloma/CNV complex was observed over the following weeks (Figure 2, E and F).
Case 3 A 20-year-old man was referred with progressive loss of vision in the left eye for 2 months. Except for contact with dogs and cats, his medical history was unremarkable. A presumed diagnosis of DUSN was made. The visual acuity was 20/400, and there was a relative afferent pupillary defect in this eye. The right eye was normal. Biomicroscopy confirmed the diagnosis of active late-stage DUSN based on signs of vitritis, optic atrophy, narrowing of vessels, RPE degeneration, and multifocal active white spots in the inferior, midperipheral, temporal quadrant. In this area, a motile 500-mm to 600-mm subretinal worm was found and immediately surrounded by laser to watch its local reaction (Figure 3A). Confluent laser was then applied to destroy the worm (Figure 3B) associated with a 7-day cycle of oral thiabendazole (1.5 g) and steroids (30 mg). After 1 week, the patient reported improvement of his vision (20/100). There was regression of the vitritis and the active retinal lesions. After 2 weeks, a new granulomatous-like retinal lesion was observed outside from the previous site of laser treatment. This lesion had a thin hemorrhagic halo and was located inferotemporally to the macular area. An optical coherence tomography scan through this lesion confirmed its granulomatous appearance confined to superficial layers of the retina (Figure 3C). A presumptive diagnosis of an active granulomatous toxocara reaction was made and reinforced by a positive ELISA (160). The patient was treated with a 30-day treatment with single oral albendazole (400 mg/d). After 1 month of treatment, his visual acuity remained 20/100, and the active granulomatous lesion had regressed (Figure 3D).
Fig. 2. Case 2. A, Color photograph of the left eye at presentation shows a whitish yellow mass beneath the macula associated with subretinal fluid and exudates (inferior arrow). Note the presence of a small, calcified, retinal, granulomatous lesion superiorly to the disk in this eye (superior arrow). B, An OCT line through the active macular lesion revealed a highly reflective granuloma-like lesion protruding above the RPE and surrounded by subretinal fluid. C, Similar findings without subretinal fluid were found for the hyperreflective, calcified, extramacular lesion. D, Early and late-phase angiograms of the active macular lesion showed features of a classic CNV. E, F, Note the regression of the macular lesion on the color photograph (arrow) and the corresponding OCT after 3 months of treatment.
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Fig. 3. Case 3. A, Color photograph of the left eye at presentation showing signs of active late-stage DUSN with optic atrophy, narrowing of vessels, RPE degeneration, and inferior, temporal, retinal, active white spots. Note the motile 500-mm to 600-mm subretinal worm surrounded by laser in the inferior midperipheral retina (black arrow). B, Note the confluent complement laser to destroy the worm after a few minutes of observation. C, After 2 weeks, outside the area of the laser treatment, a new granulomatous-like retinal lesion with a thin hemorrhagic halo was found inferotemporally to the macula (black arrow). An OCT scan through this lesion showed its granulomatous appearance confined to superficial layers of the retina. D, Color photograph and corresponding OCT showing resolution of the active granulomatous lesion after 1 month of treatment.
Discussion The diagnosis of presumed ocular toxocariasis is usually based on the presence of a chorioretinal granuloma in the posterior eye segment in the presence of positive serology.1,4 Standard ELISA tests use the antigen prepared with T. canis and when positive show a high cross-reactivity between T. canis and T. cati.2 Therefore, it is important to be aware that ocular toxocariasis can also be caused by T. cati. Apart from the fundoscopic findings, the present three cases were exposed to potential contaminated soils by dogs and cats. However, in all of them, the ELISA tests using T. canis revealed marginal antibody production.1,2 Unfortunately, not performed, a search for intraocular immunoglobulins against both T. canis and T. cati could be of value, confirming the two agents and their differentiation in these patients.1 We wonder if the fundoscopic lesions we found in Cases 1 and 2 were the anatomic representations of eosinophilic granuloma-like lesions as a line of immunologic defense against an infecting toxocara organism originating from the choroid. The resultant chorioretinal granulomatous reaction
might regress slowly or encyst in the subretinal pigment epithelial space.3,7 Following this proposed mechanism of disease, we believe that Cases 1 and 2 have initially failed to control the infection, giving access to the parasite to inner portions of the retina.6 In Case 1, the resultant local pearl-like structure that emerged at the retina surface might represent a “larval encystment response” spontaneous or secondary to treatment before its complete disintegration. Differently, in Case 2, the envelopment of the invading parasite by the RPE could have resulted in its destruction as a granulomatous lesion (or subretinal neovascular membrane) above the RPE in the macular area.3,4,7 Presumably, this invading parasite originating from the short ciliary circulation was the cause of the suprapapillary retinal lesions before its migration to the macula. This assumption was based on pathologic involvement of other human tissues in toxocariasis. For example, it has been described that toxocara antigens left in the liver during its tissue migration are related to the development of multiple and isolated eosinophil-rich granulomatous lesions.2 Finally, in Case 3, the fundoscopic and tomographic findings that resulted from the treatment
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of the mobile subretinal worm reopened the possibility of toxocariasis being involved in the pathogenesis of DUSN in Brazil.5,8,9 The exact retinal layer in which a DUSN worm moves has not yet been determined.6 In patients with DUSN, we believe that a toxocara larva originating from the choroid is able to cross the RPE, intactly, and move freely in the subretinal space during many years.5,8,9 The reason why these patients, usually, do not develop a reactive chorioretinal granuloma against the infecting worm is unknown. In Case 3, the appearance of a new granulomatous-like retinal lesion surrounded by blood was noticed 2 weeks after treatment to destroy a motile worm with laser and oral anthelmintic medication. Optical coherence tomography confirmed the granulomatous nature of this lesion confined to the inner layers of the retina inferotemporally to the macula. Because this granulomatous lesion was first noticed outside the area of laser treatment, the possibility of choroidal neovascularization7 was not seriously considered in this case. As not infrequently observed in cases of DUSN,5,8,9 we assume that the worm was undertreated in this case. However, this type of treatment could have stimulated a presumed subretinal toxocara to migrate inside the retina before disintegrating in its superficial layers.6 In summary, we present clinical and tomographic features of the migrating nature of presumed toxocara larvae in the posterior eye segment of three young Brazilian patients. The chances to document these inusitated findings in these three unrelated patients have permitted us to propose new mechanisms of host infections related to ocular toxocariasis.
Key words: migrating toxocara larva, granulomatous lesion, anthelmintics, diffuse unilateral subacute neuroretinitis, idiopathic choroidal neovascularization, punctate inner choroidopathy. References 1. Sakai R, Kawashima H, Shibui H, et al. Toxocara cati-induced ocular toxocariasis. Arch Ophthalmol 1998;12:1686–1687. 2. Brito T, Chieffi PP, Peres B, et al. Immunohistochemical detection of toxocara antigens in human liver biopsies. Int J Surg Pathol 1994;2:117–123. 3. Higashide T, Akao N, Shirao E, et al. Optical coherence tomographic and angiographic findings of a case with subretinal toxocara granuloma. Am J Ophthalmol 2003;1:188–190. 4. Lida T, Hagimura N, Sato T, et al. Optical coherence tomographic features of idiopathic submacular choroidal neovascularization. Am J Ophthalmol 2000;130:763–768. 5. Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology 1995;102:1183–1186. 6. Suzuki T, Joko T, Akao N, et al. Following the migration of a toxocara larva in the retina by optical coherence tomography and fluorescein angiography. Ophthalmology 2005;49:159–161. 7. Machida S, Fujiwara T, Murai K, et al. Idiopathic choroidal neovascularization as an early manifestation of inflammatory chorioretinal diseases. Retina 2008;28:703–710. 8. Souza EC, Abujamra S, Nakasima Y, Gass JD. Diffuse unilateral subacute neuroretinitis: first patient with documented nematodes in both eyes. Arch Ophthalmol 1999;117: 1349–1351. 9. Souza EC, Casella AM, Nakasima Y, et al. Clinical features and outcomes of patients with diffuse unilateral subacute neuroretinitis treated with oral albendazole. Am J Ophthalmol 2005;140:437–445.
Purpose: To document the intraretinal migration of presumed toxocara larvae mimicking punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis. Methods: Sequential color photographs, fluorescein angiograms, and optical coherence tomography were performed in three unrelated adult patients with presumed ocular toxocariasis. Results: Characteristic fundoscopic manifestations simulating punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis were reported in these patients, respectively. Conclusion: Presumed toxocara larvae must be included as a potential cause of different inflammatory diseases as a result of its migration through the retinal layers. RETINAL CASES & BRIEF REPORTS 6:430–434, 2012
larvae travel throughout the small animals’ intestines where the adult worms produce eggs. Several thousand eggs are produced per day and are shed in an infected animal’s feces into the soil where they can live dormant for several months to years.1 Similarly, in humans, the eggs hatch in the intestines and the larvae penetrate the intestinal wall entering the circulation. As an intermediate host for Toxocara spp., the larvae cannot develop into adult worms or multiply in an infected human. The disease process is noticed only when an immunologic reaction is activated in the host.1 For example, when second-stage and third-stage larvae enter the eye through the blood circulation, they typically tend to migrate from the choroidal vessels, across the retina, toward the vitreous cavity. This migrating behavior of toxocara can be associated with an eosinophilic type of granulomatous response in these ocular tissues.3 We believe to have examined three unrelated young Brazilian patients with this
From the *Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil; †Department of Ophthalmology, Universidade de Campinas; and ‡Department of Ophthalmology, Hospital de Olhos Niterói, Niteroi, Brazil.
T
oxocara canis and Toxocara cati are nematodes known to cause toxocariasis in dogs and cats, as well as ocular toxocariasis in humans.1,2 Both nematodes are accidentally contracted in humans by eating eggs in dirt and by contacting an infected animal.1 Toxocara spp., a roundworm parasite, infects puppies and kittens that ingest the eggs or larvae. The Presented as a Scientific Poster at the Retinal Congress, New York, NY, September 30-October 4, 2009. The authors declare no conflict of interest. Reprint requests: Eduardo C. De Souza, MD, PhD, Department of Ophthalmology, Universidade Federal de São Paulo (UNIFESP), Rua Mato Grosso 306 4th 411, São Paulo, 01239 040 Brazil; e-mail: [email protected]
430
DOCUMENTATION OF TOXOCARA MIGRATION
mechanism of ocular toxocariais mimicking punctate inner choroidopathy, idiopathic choroidal neovascularization, and diffuse unilateral subacute neuroretinitis (DUSN). Case Reports Case 1 A 23-year-old healthy woman presented with reduced central vision and metamorphopsia in the right eye. She was initially diagnosed with choroidal neovascularization (CNV) secondary to punctate inner choroidopathy. Visual acuity was 20/40 with −1.00
431 (−1.00 · 75), and there was no inflammatory cells in the vitreous. The left eye was normal. Biomicroscopy showed a 1DD yellowish elevated and hemorrhagic lesion superior nasally to the macula in the right eye. Multiple white punctate lesions were seen surrounding the macula temporally (Figure 1A). Fluorescein angiography confirmed the apparent classic CNV aspect of the hemorrhagic lesion and staining of the focal lesions and optic nerve (Figure 1C). Corresponding to the hemorrhagic lesion, optical coherence tomography revealed a protruded granulomatous lesion above the retinal pigment epithelium (RPE) and under the external limitant membrane associated with a shallow retinal detachment extending to the center of the macula (Figure 1B). Over the subsequent days, there was progression of the surrounding subretinal fluid associated with exudates in the macula (Figure 1D) and extension of the
Fig. 1. Case 1. A, Color photograph of the right eye at presentation shows a yellowish hemorrhagic lesion superior nasally to the macula (black arrow). Multiple white punctate lesions were seen surrounding the macula temporally (white arrow). B, An optical coherence tomographic line through the lesion revealed a hyperreflective granulomatous lesion above the RPE and under the external limiting membrane. C, Fluorescein angiogram of the lesion demonstrating features of classic CNV and staining of the focal lesions and optic nerve. D, Note the presence of subretinal fluid and exudates in the macula 1 week after observation. E, A corresponding OCT examination demonstrated extension of the granulomatous lesion to inner portions of the retina. F, Two weeks after treatment, the lesion regressed and a small , translucent, pearl-like structure was observed in the surface of the retina (black arrow). G, A corresponding OCT examination confirmed a further superficial extension of the hyperreflective granulomatous lesion. H, Color photograph showing shrinkage and consolidation of the granulomatous lesion after 1 year of follow-up.
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tomographic granuloma to inner portions of the retina (Figure 1E). A diagnosis of presumed toxocariasis was made and reinforced by a history of recent exposure to kittens and positive immunoglobulin G serologic antibody titer by enzyme-linked immunosorbent assay (ELISA) (88). She was given a 10-day course of Albendazole (400 mg) and oral steroid (20 mg). The serous retinal detachment gradually decreased and vision improved to 20/25. Surprisingly, in the area corresponding to the previous CNV, a small translucent “pearl-like” structure was observed emerging in the superficial layers of the retina (Figure 1, F and G). During the subsequent weeks, there was a progressive shrinkage and consolidation of the granulomatous lesion in that eye (Figure 1H). Visual acuity remained 20/20 without distortion.
Case 2 A 13-year-old boy presented with loss of central vision in the left eye for 3 months. Except for direct contact with cats, the patient’s medical history was unremarkable. He was referred with the diagnosis of idiopathic CNV in his left eye. Visual acuity was 20/80, and there were no inflammatory cells in the vitreous. The right eye was normal. Biomicroscopy showed a whitish yellow mass beneath the macula associated with subretinal fluid and exudates in the left eye. Outside the macula, a small whitish calcified lesion and focal areas of hyperpigmentation were seen superiorly to the disk in this eye (Figure 2A). Angiography revealed a hypofluorescent rim surrounding the CNV-like hyperfluorescent lesion in the macula, indicating the envelopment of the CNV by the RPE (Figure 2D). An optical coherence tomography line through the active macular lesion revealed a highly reflective granulomalike lesion protruding above the RPE and surrounded by subretinal fluid (Figure 2C). Similar findings without subretinal fluid were found for the hyperreflective, calcified, extramacular lesion (Figure 2B). A diagnosis of presumed toxocariasis was mainly
based on the granulomatous aspect of these lesions in this case (positive immunoglobulin G–ELISA of 116). The patient was given a 10-day course of albendazole (400 mg) and oral steroid (20 mg). Regression of the macular granuloma/CNV complex was observed over the following weeks (Figure 2, E and F).
Case 3 A 20-year-old man was referred with progressive loss of vision in the left eye for 2 months. Except for contact with dogs and cats, his medical history was unremarkable. A presumed diagnosis of DUSN was made. The visual acuity was 20/400, and there was a relative afferent pupillary defect in this eye. The right eye was normal. Biomicroscopy confirmed the diagnosis of active late-stage DUSN based on signs of vitritis, optic atrophy, narrowing of vessels, RPE degeneration, and multifocal active white spots in the inferior, midperipheral, temporal quadrant. In this area, a motile 500-mm to 600-mm subretinal worm was found and immediately surrounded by laser to watch its local reaction (Figure 3A). Confluent laser was then applied to destroy the worm (Figure 3B) associated with a 7-day cycle of oral thiabendazole (1.5 g) and steroids (30 mg). After 1 week, the patient reported improvement of his vision (20/100). There was regression of the vitritis and the active retinal lesions. After 2 weeks, a new granulomatous-like retinal lesion was observed outside from the previous site of laser treatment. This lesion had a thin hemorrhagic halo and was located inferotemporally to the macular area. An optical coherence tomography scan through this lesion confirmed its granulomatous appearance confined to superficial layers of the retina (Figure 3C). A presumptive diagnosis of an active granulomatous toxocara reaction was made and reinforced by a positive ELISA (160). The patient was treated with a 30-day treatment with single oral albendazole (400 mg/d). After 1 month of treatment, his visual acuity remained 20/100, and the active granulomatous lesion had regressed (Figure 3D).
Fig. 2. Case 2. A, Color photograph of the left eye at presentation shows a whitish yellow mass beneath the macula associated with subretinal fluid and exudates (inferior arrow). Note the presence of a small, calcified, retinal, granulomatous lesion superiorly to the disk in this eye (superior arrow). B, An OCT line through the active macular lesion revealed a highly reflective granuloma-like lesion protruding above the RPE and surrounded by subretinal fluid. C, Similar findings without subretinal fluid were found for the hyperreflective, calcified, extramacular lesion. D, Early and late-phase angiograms of the active macular lesion showed features of a classic CNV. E, F, Note the regression of the macular lesion on the color photograph (arrow) and the corresponding OCT after 3 months of treatment.
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Fig. 3. Case 3. A, Color photograph of the left eye at presentation showing signs of active late-stage DUSN with optic atrophy, narrowing of vessels, RPE degeneration, and inferior, temporal, retinal, active white spots. Note the motile 500-mm to 600-mm subretinal worm surrounded by laser in the inferior midperipheral retina (black arrow). B, Note the confluent complement laser to destroy the worm after a few minutes of observation. C, After 2 weeks, outside the area of the laser treatment, a new granulomatous-like retinal lesion with a thin hemorrhagic halo was found inferotemporally to the macula (black arrow). An OCT scan through this lesion showed its granulomatous appearance confined to superficial layers of the retina. D, Color photograph and corresponding OCT showing resolution of the active granulomatous lesion after 1 month of treatment.
Discussion The diagnosis of presumed ocular toxocariasis is usually based on the presence of a chorioretinal granuloma in the posterior eye segment in the presence of positive serology.1,4 Standard ELISA tests use the antigen prepared with T. canis and when positive show a high cross-reactivity between T. canis and T. cati.2 Therefore, it is important to be aware that ocular toxocariasis can also be caused by T. cati. Apart from the fundoscopic findings, the present three cases were exposed to potential contaminated soils by dogs and cats. However, in all of them, the ELISA tests using T. canis revealed marginal antibody production.1,2 Unfortunately, not performed, a search for intraocular immunoglobulins against both T. canis and T. cati could be of value, confirming the two agents and their differentiation in these patients.1 We wonder if the fundoscopic lesions we found in Cases 1 and 2 were the anatomic representations of eosinophilic granuloma-like lesions as a line of immunologic defense against an infecting toxocara organism originating from the choroid. The resultant chorioretinal granulomatous reaction
might regress slowly or encyst in the subretinal pigment epithelial space.3,7 Following this proposed mechanism of disease, we believe that Cases 1 and 2 have initially failed to control the infection, giving access to the parasite to inner portions of the retina.6 In Case 1, the resultant local pearl-like structure that emerged at the retina surface might represent a “larval encystment response” spontaneous or secondary to treatment before its complete disintegration. Differently, in Case 2, the envelopment of the invading parasite by the RPE could have resulted in its destruction as a granulomatous lesion (or subretinal neovascular membrane) above the RPE in the macular area.3,4,7 Presumably, this invading parasite originating from the short ciliary circulation was the cause of the suprapapillary retinal lesions before its migration to the macula. This assumption was based on pathologic involvement of other human tissues in toxocariasis. For example, it has been described that toxocara antigens left in the liver during its tissue migration are related to the development of multiple and isolated eosinophil-rich granulomatous lesions.2 Finally, in Case 3, the fundoscopic and tomographic findings that resulted from the treatment
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RETINAL CASES & BRIEF REPORTS´ 2012 VOLUME 6 NUMBER 4
of the mobile subretinal worm reopened the possibility of toxocariasis being involved in the pathogenesis of DUSN in Brazil.5,8,9 The exact retinal layer in which a DUSN worm moves has not yet been determined.6 In patients with DUSN, we believe that a toxocara larva originating from the choroid is able to cross the RPE, intactly, and move freely in the subretinal space during many years.5,8,9 The reason why these patients, usually, do not develop a reactive chorioretinal granuloma against the infecting worm is unknown. In Case 3, the appearance of a new granulomatous-like retinal lesion surrounded by blood was noticed 2 weeks after treatment to destroy a motile worm with laser and oral anthelmintic medication. Optical coherence tomography confirmed the granulomatous nature of this lesion confined to the inner layers of the retina inferotemporally to the macula. Because this granulomatous lesion was first noticed outside the area of laser treatment, the possibility of choroidal neovascularization7 was not seriously considered in this case. As not infrequently observed in cases of DUSN,5,8,9 we assume that the worm was undertreated in this case. However, this type of treatment could have stimulated a presumed subretinal toxocara to migrate inside the retina before disintegrating in its superficial layers.6 In summary, we present clinical and tomographic features of the migrating nature of presumed toxocara larvae in the posterior eye segment of three young Brazilian patients. The chances to document these inusitated findings in these three unrelated patients have permitted us to propose new mechanisms of host infections related to ocular toxocariasis.
Key words: migrating toxocara larva, granulomatous lesion, anthelmintics, diffuse unilateral subacute neuroretinitis, idiopathic choroidal neovascularization, punctate inner choroidopathy. References 1. Sakai R, Kawashima H, Shibui H, et al. Toxocara cati-induced ocular toxocariasis. Arch Ophthalmol 1998;12:1686–1687. 2. Brito T, Chieffi PP, Peres B, et al. Immunohistochemical detection of toxocara antigens in human liver biopsies. Int J Surg Pathol 1994;2:117–123. 3. Higashide T, Akao N, Shirao E, et al. Optical coherence tomographic and angiographic findings of a case with subretinal toxocara granuloma. Am J Ophthalmol 2003;1:188–190. 4. Lida T, Hagimura N, Sato T, et al. Optical coherence tomographic features of idiopathic submacular choroidal neovascularization. Am J Ophthalmol 2000;130:763–768. 5. Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology 1995;102:1183–1186. 6. Suzuki T, Joko T, Akao N, et al. Following the migration of a toxocara larva in the retina by optical coherence tomography and fluorescein angiography. Ophthalmology 2005;49:159–161. 7. Machida S, Fujiwara T, Murai K, et al. Idiopathic choroidal neovascularization as an early manifestation of inflammatory chorioretinal diseases. Retina 2008;28:703–710. 8. Souza EC, Abujamra S, Nakasima Y, Gass JD. Diffuse unilateral subacute neuroretinitis: first patient with documented nematodes in both eyes. Arch Ophthalmol 1999;117: 1349–1351. 9. Souza EC, Casella AM, Nakasima Y, et al. Clinical features and outcomes of patients with diffuse unilateral subacute neuroretinitis treated with oral albendazole. Am J Ophthalmol 2005;140:437–445.
